Value of Preoperative Hematological Parameters in the Prognosis of Gastric Cancer Patients Undergoing a Total Gastrectomy.

OBJECTIVE: This study aimed to evaluate the relationships between the albumin/globulin ratio (AGR), neutrophil/lymphocyte ratio (NLR), and platelet/lymphocyte ratio (PLR) and clinicopathological information for gastric cancer patients. In addition, the prognostic values of these hematological parameters for resectable gastric cancer patients undergoing a total gastrectomy were determined. METHODS: A total of 245 patients with gastric cancer who underwent a total gastrectomy at our hospital between January 1, 2005, and December 30, 2015, were enrolled into this study. The preoperative AGR, NLR, and PLR in the serum samples of the patients were measured. The relationships between the hematological parameters and the disease-free survival (DFS) as well as overall survival (OS) were analyzed by statistical analysis. RESULTS: The cutoff values of AGR, NLR, and PLR were 1.57, 3.5, and 193, respectively. Univariate analyses demonstrated that a low AGR, a high NLR, and a high PLR were significant risk factors for a poor prognosis. According to multivariate analysis, a high PLR was found to be independently associated with a poor survival. Additionally, when age was considered as a stratified factor, univariate analyses demonstrated that a low AGR had the tendency to be correlated with a shorter DFS in nonelderly patients (<65 years old). A low AGR was significantly correlated with a shorter DFS and OS in elderly patients (≥65 years old). CONCLUSION: AGR, NLR, and PLR are independent risk factors associated with a poor gastric cancer survival by univariate analysis, and AGR is an independent risk factor for predicting DFS and OS in elderly patients (≥65 years old) with gastric cancer after total gastrectomy.

BCR/ABL mRNA targeting small interfering RNA effects on proliferation and apoptosis in chronic myeloid leukemia.

BACKGROUND: To investigate the effects of small interference RNA (siRNA) targeting BCR/ABL mRNA on proliferation and apoptosis in the K562 human chronic myeloid leukemia (CML) cell line and to provide a theoretical rationale and experimental evidence for its potential clinical application for anti-CML treatment. MATERIALS AND METHODS: The gene sequence for BCR/ABL mRNA was found from the GeneBank. The target gene site on the BCR/ABL mRNA were selected according to Max-Planck-Institute (MPI) and rational siRNA design rules, the secondary structure of the candidate targeted mRNA was predicted, the relevant thermodynamic parameters were analyzed, and the targeted gene sequences were compared with BLAST to eliminate any sequences with significant homology. Inhibition of proliferation was evaluated by MTT assay and colony-formation inhibiting test. Apoptosis was determined by flow cytometry (FCM) and the morphology of apoptotic cells was identified by Giemsa-Wright staining. Western blotting was used to analyze the expression of BCR/ABL fusion protein in K562 cells after siRNA treatment. RESULTS: The mRNA local secondary structure calculated by RNA structure software, and the optimal design of specific siRNA were contributed by bioinformatics rules. Five sequences of BCR/ABL siRNAs were designed and synthesized in vitro. Three sequences, siRNA1384, siRNA1276 and siRNA1786, which showed the most effective inhibition of K562 cell growth, were identified among the five candidate siRNAs, with a cell proliferative inhibitory rate nearly 50% after exposure to 12.5 nmol/L~50 nmol/L siRNA1384 for 24,48 and 72 hours. The 50% inhibitory concentrations (IC50) of siRNA1384, siRNA1276 and siRNA1786 for 24 hours were 46.6 nmol/L, 59.3 nmol/L and 62.6 nmol/L, respectively, and 65.668 nmol/L, 76.6 nmol/L, 74.4 nmol/L for 72 hours. The colony-formation inhibiting test also indicated that, compared with control, cell growth of siRNA treated group was inhibited. FCM results showed that the rate of cell apoptosis increased 24 hours after transfecting siRNA. The results of annexinV/PI staining indicated that the rate of apoptosis imcreased (1.53%, 15.3%, 64.5%, 57.5% and 21.5%) following treamtne with siRNAs (siRNA34, siRNA372, siRNA1384, siRNA1276 and siRNA1786). Morphological analysis showed td typical morphologic changes of apoptosis such as shrunken, fragmentation nucleus as well as "apoptotic bodies" after K562 cell exposure to siRNA. Western blot analysis showed that BCR/ABL protein was reduced sharply after a single dose of 50 nmol/L siRNA transfection. CONCLUSIONS: Proliferation of K562 cells was remarkbly inhibited by siRNAs (siRNA1384, siRNA1276 and siRNA1786) in a concentration-dependent manner in vitro, with effective induction of apoptosis at a concentration of 50 nmol/L. One anti-leukemia mechanism in K562 cells appeared that BCR/ABL targeted protein was highly down-regulated. The siRNAs (siRNA1384, siRNA1276 and siRNA1786) may prove valuable in the treatment of CML.

Matrix metalloproteinase-9 was involved in the immuno-modulatory defect of mesenchymal stem cell from chronic myeloid leukemia patients.

BACKGROUND: Overwhelming evidences on chronic myeloid leukemia (CML) indicate that patients harbor quiescent CML stem cells that are responsible for blast crisis. While the hematopoietic stem cell (HSC) origin of CML was first suggested over 30 years ago, recently CML-initiating cells beyond HSCs are also being investigated. METHODS: We have previously isolated fetal liver kinase-1-positive (Flk1(+)) cells carrying the BCR/ABL fusion gene from the bone marrow of Ph(+) patients with hemangioblast property. In this study, we isolated CML patient-derived Flk1(+)CD31(-)CD34(-) mesenchymal stem cells (MSCs) and detected their biological characteristics and immunological regulation using fluorescence in situ hybridization (FISH) analysis, fluorescence activated cell sorting (FACS), enzyme-linked immunoadsorbent assay, mixed lymphocyte reaction assays; then we compared these characters with those of the healthy donors. RESULTS: CML patient-derived Flk1(+)CD31(-)CD34(-) MSCs had normal morphology, phenotype and karyotype while appeared impaired in immuno-modulatory function. The capacity of patient Flk1(+)CD31(-)CD34(-) MSCs to inhibit T lymphocyte activation and proliferation was impaired in vitro. CONCLUSIONS: CML patient-derived MSCs have impaired immuno-modulatory functions, suggesting that the dysregulation of hematopoiesis and immune response may originate from MSCs rather than hematopoietic stem cells (HSCs). MSCs might be a potential target for developing efficacious treatment for CML.

[Progress of study on the roles of matrix metalloproteinases in the pathogenesis of hematologic malignancies -- review].

Matrix metalloproteinases (MMPs) have the ability to degrade extracellular matrix components. They abnormally express in a variety of solid tumors and hematologic malignancies, and play an important role in tumor invasion and metastasis through extracellular matrix degradation, which closely relates with the progression and prognosis of the malignant disease. This article reviews progress of study on the mechanism of MMP underlying the pathogenesis of hematologic malignancies, including structure of MMP, regulation mechanism of MMP and its relation with proliferation and differentiation of hematopoietic stem cells (HSC), angiogenesis and tumor immunology and so on.