Genomic risk of hepatitis C-related hepatocellular carcinoma

To identify the genetic susceptibility factor(s) for hepatitis C virus-induced hepatocellular carcinoma (HCV-induced HCC), we conducted a genome-wide association study using 432,703 autosomal SNPs in 721 individuals with HCV-induced HCC (cases) and 2890 HCV-negative controls of Japanese origin. Eight SNPs that showed possible association (P <1 10(?5)) in the genome-wide association study were further genotyped in 673 cases and 2596 controls. We found a previously unidentified locus in the 50 flanking region of MICA on 6p21.33 (rs2596542, P(combined) = 4.21 10(?13), odds ratio = 1.39) to be strongly associated with HCV induced HCC. Subsequent analyses using individuals with chronic hepatitis C (CHC) indicated that this SNP is not associated with CHC susceptibility (P = 0.61) but is significantly associated with progression from CHC to HCC (P = 3.13 10(?8)). We also found that the risk allele of rs2596542 was associated with lower soluble MICA protein levels in individuals with HCV-induced HCC (P = 1.38 10(?13)).     

Addition of iron to erythropoiesis-stimulating agents in cancer patients: a meta-analysis of randomized trials

Background  

Iron supplementation could improve the hematopoietic response of erythropoiesis-stimulating agents (ESAs) used for chemotherapy-induced anemia.     

Pegylated interferon for chronic hepatitis C in children affects growth and body composition: results from the pediatric study of hepatitis C (PEDS-C) trial

Weight loss and changes in growth are noted in children treated with interferon alpha (IFN-α). The aim of this study was to prospectively determine changes in weight, height, body mass index (BMI), and body composition during and after treatment of children with hepatitis C virus (HCV). Children treated with pegylated interferon alpha-2a (Peg-IFN-α2a) ± ribavirin in the Pediatric Study of Hepatitis C (PEDS-C) trial underwent anthropometric measurements, dual-energy X-ray absorptiometry scan, as well as dietary and activity assessments during and after treatment. One hundred and fourteen (55% male) children, with a mean age of 11 ± 3 years, were randomized, and 107 received treatment for at least 24 weeks. Subjects were divided into three groups according to duration of treatment: 24 (N = 14), 48 (N = 82), or 72 (N = 11) weeks. Decrements of up to 0.50 z score were observed for weight, height, and BMI while on therapy among all groups (P ≤ 0.01, compared to baseline). In the group treated for 48 weeks, 29 (33%) subjects had greater than 0.5-unit decrement in height-for-age z (HAZ) score. Though weight-for-age and BMI z scores returned to baseline after cessation of therapy, mean HAZ score was slower to rebound, still lower than baseline at 96 weeks post-therapy for the long-treatment duration group (P = 0.03) and lower than baseline in most children treated for 48 weeks. Percent body fat, fat-free mass z scores, and triceps skinfold z scores decreased with therapy. Dietary energy intake and levels of physical activity did not change during treatment. CONCLUSIONS: Peg-IFN-α2a was associated with significant changes in body weight, linear growth, BMI, and body composition in children. These effects were generally reversible with cessation of therapy, although HAZ scores had not returned to baseline after 2 years of observation in many. Longer term growth data are needed among children treated for chronic HCV.     

Improving outcomes in umbilical cord blood transplantation: State of the art

Only 30% of patients who require an allogeneic hematopoietic cell transplant will have a HLA matched sibling donor. Many patients, particularly those patients with diverse racial and ethnic backgrounds, may not be able to identify a suitably matched unrelated donor. Over 25,000 umbilical cord blood transplant procedures have been performed in the last 25 years. Considerable challenges exist in defining the appropriate conditioning regimen and graft vs host disease prophylaxis, surmounting issues of cell dose and delayed engraftment, and improving immune recovery. In this review, we discuss strategies to improve umbilical cord blood transplant outcomes, focusing on cord blood unit selection, expansion, and homing efficiency.     

Treatment with high-dose simvastatin inhibits geranylgeranylation in AML blast cells in a subset of AML patients

It is currently unknown whether the in?vitro effects observed with statins in acute myeloid leukemia (AML) cells, including lowering of cholesterol, inhibition of isoprenylation, and sensitization to chemotherapy, also occur in?vivo. Therefore, AML mononuclear cells (MNCs) were isolated from 12 patients before and after 7 days of high-dose (7.5-15 mg/kg/day) simvastatin treatment. Parallel mouse studies were performed to have, in addition to AML cells, access to liver tissue, a major target of statins. Serum cholesterol levels were lowered by simvastatin in all patients, however, only limited changes in the messenger RNA expression of cholesterol metabolism genes were seen in patient and mouse MNCs compared to murine liver cells. Still, two out of seven patients displayed an increased in?vitro chemosensitivity of their AML cells upon simvastatin treatment. Gene set enrichment analysis on microarray data of AML patient cells and Western blot analysis for the isoprenylated proteins DnaJ and Rap1 on murine and AML patient MNCs demonstrated that in?vivo simvastatin treatment resulted in inhibition of geranylgeranylation in murine MNCs and in a subset of patient AML MNCs. In summary, our data demonstrate that simvastatin treatment results in chemosensitization and inhibition of geranylgeranylation in AML cells of a subset of patients.