The correlation between genetic variation and expression of DLL1 gene and bone marrow suppression after neoadjuvant chemotherapy for breast cancer / 中华内分泌外科杂志

Objective:To investigate the effects of two SNP sites of delta-like ligand protein-1 (DLL1) gene rs2738822 (C>T) and rs9459988 (T>G) and gene expression on bone marrow suppression after neoadjuvant chemotherapy for breast cancer.Methods:Breast cancer patients who received neoadjuvant chemotherapy were selected as study subjects, including 90 patients with severe bone marrow suppression and 72 patients with mild bone marrow suppression. Patient’s demographic characteristics and laboratory test indicators were collected. Two SNP sites of DLL1, rs2738822 and rs9459988, were genotyped by capillary electrophoresis and section analysis (SNaPshot) . The relative mRNA expression of DLL1 gene was detected by quantitative reverse polymerase chain reaction (QRT-PCR) method.Results:For The rs2738822 of DLL1 gene, the genotype distribution difference between severe and mild bone marrow suppression groups was statistically significant ( χ2=8.622, P=0.013) . Compared with CC genotype, CT and TT genotype carriers had a higher risk of severe bone marrow suppression, with an OR value of 2.746 (1.335-6.882) and 3.054 (1.282-8.143) , respectively. The dominant model results showed that TT OR CT carriers had a significantly higher risk of severe bone marrow suppression than THOSE with CC genotype [ OR=2.976 (1.231-4.963) ]. For rs9459988, there was no significant difference in genotype distribution between severe bone marrow suppression group and mild bone marrow suppression group ( χ2=2.149, P=0.342) . Results of the dominant model showed that TG or GG carriers had a significantly higher risk of severe bone marrow suppression than TT carriers, with an OR value of 2.046 (1.053-5.611) . The relative mRNA expression level of DLL1 gene was 1.15±0.23 in patients with severe bone marrow suppression, which was significantly lower than that in patients with mild bone marrow suppression (2.64±0.51) ( t=6.381, P<0.001) . For rs2738822, with the increase of T allele, the relative mRNA expression level of DLL1 gene decreased gradually ( P<0.05) . For rs9459988, the relative mRNA expression level of DLL1 gene in patients with mutant allele G was also significantly lower than that in wild-type CC carriers ( P<0.05) . Conclusion:Mutations of DLL1 genes rs2738822 and rs9459988 are related to the occurrence of severe bone marrow suppression after neoadjuvant chemotherapy for breast cancer, and can be used as a genetic marker to predict the degree of bone marrow suppression after neoadjuvant chemotherapy for breast cancer patients.

Comparison of outcomes of adult acute lymphoblastic leukemia patients underwent autologous and allogeneic hematopoietic stem cell transplantation / 中华血液学杂志

<p><b>OBJECTIVE</b>To compare the outcomes of adult patients with acute lymphoblastic leukemia (ALL) who underwent autologous hematopoietic stem cell transplantation (auto-HSCT) and allogeneic hematopoietic stem cell transplantation (allo-HSCT).</p><p><b>METHODS</b>From Jan 2007 to Dec 2010, 106 adult ALL patients were retrospectively divided into two groups, 50 in auto-HSCT group and 56 in allo-HSCT group. Auto-HSCT group included 21 patients with high-risk, 46 patients in CR1 and 4 cases in CR2. All the 50 patients had negative minimal residual disease (MRD) prior to HSCT. Allo-HSCT group included 44 patients with high risk, 51 patients in CR1 and 5 cases in CR2, 15 patients with positive MRD before allo-HSCT. response, regulatory T cells (Treg), cytokines levels and treatment-related adverse effects were observed.</p><p><b>RESULTS</b>Of the total 106 patients, 29 patients relapsed at a medium follow-up of 22.9(0.8-63.3) months. The 3-year cumulative relapse rate (RR) was (29.9±8.0) % in auto-HSCT group and (32.7±6.8) % in allo-HSCT group. There were no significant differences in RR and overall survival (OS) between auto-HSCT and allo-HSCT groups, even of stratified risk groups. In standard risk group, 3-year OS was (77.1±13.2) % in auto-HSCT group and (90.9±8.7) % in allo-HSCT group (P=0.739). In high-risk group, 3-year OS was (68.7±10.8) % after auto-HSCT and (45.2±8.5) % after allo-HSCT (P=0.094).</p><p><b>CONCLUSION</b>Due to acceptable RR and OS, adult ALL patients with no MRD before HSCT showed favorable survival. Auto-HSCT may be a considerable choice for adult ALL patients with negative MRD when lacking of donors for allo-HSCT.</p>

Effect of indomethacin on the migration of breast cancer cells in vitro / 国际生物医学工程杂志

ObjectiveTo observe the effect of indomethacin on the migration of breast cancer cell line MCF-7 in vitro and investigate the mechanism involved.MethodsThe migration of MCF-7 cell line stimulated with or without indomethacin were tested using transwell plates consisting upper and lower chambers separated by Millipore polycarbonate membrance filters with 8 μm pore sizes; the levels of chemokine receptor 4(CXCR4),cyclooxygenase(COX-2),epidermal growth factor receptor(EGFR) and vascular endothelial growth factor(VEGF)expression in MCF-7 cell line were detected by flow cytometry,Real-time PCR and ELISA,respectively.Results Indomethacin decreased the migration ability of MCF-7 cell line significandy.CXCR4 membrane expression was significantly reduced in a time-dose dependent manner,and CXCR4,COX-2 and EGFR mRNA levels were significantly downregulated after indomethacin stimulation.However,exposure to indometahcin had no major effect on VEGF production of cells.ConclusionThe downregulation of CXCR4,COX-2 and EGFR expression might be the primary mechanism involved in the inhibitory effect of indomethacin on the migration of MCF-7 cell line.