Drug Delivery Systems ; Humans ; Neoplasms ; drug therapy ; etiology ; pathology ; Neoplastic Stem Cells ; pathology ; physiology ; Neovascularization, Pathologic

Animals ; Cell Proliferation ; Disease Progression ; Endothelial Cells ; pathology ; Humans ; Indoleamine-Pyrrole 2,3,-Dioxygenase ; metabolism ; Mesenchymal Stromal Cells ; immunology ; metabolism ; pathology ; Neoplasms ; immunology ; pathology ; Neoplastic Stem Cells ; pathology ; Neovascularization, Pathologic ; pathology ; Stem Cells ; pathology ; T-Lymphocytes ; immunology ; pathology

Animals ; Apoptosis ; Cell Cycle ; Cell Differentiation ; Cell Proliferation ; Connexin 43 ; metabolism ; Humans ; Neoplasm Invasiveness ; pathology ; physiopathology ; Neoplasms ; metabolism ; pathology ; physiopathology ; Neoplastic Stem Cells ; metabolism ; pathology ; physiology ; Neovascularization, Pathologic ; metabolism ; pathology ; physiopathology ; Receptors, CXCR4 ; metabolism ; Receptors, Formyl Peptide ; metabolism ; Vascular Endothelial Growth Factor A ; metabolism

Antigens, CD34 ; genetics ; metabolism ; Capillaries ; metabolism ; pathology ; Genetic Heterogeneity ; Microcirculation ; Neoplasms ; blood supply ; Neovascularization, Pathologic ; genetics ; metabolism ; pathology ; Phenotype ; Platelet Endothelial Cell Adhesion Molecule-1 ; genetics ; metabolism

AC133 Antigen ; Animals ; Antigens, CD ; metabolism ; Cell Differentiation ; Cell Proliferation ; Drug Resistance, Neoplasm ; Glioma ; pathology ; Glycoproteins ; metabolism ; Humans ; Neoplastic Stem Cells ; metabolism ; pathology ; physiology ; Neovascularization, Pathologic ; etiology ; pathology ; Peptides ; metabolism ; Radiation Tolerance

Objective　To investigate the expression of glial fibrillary acidic protein (GFAP) gene and its significance in the process of glioma cell differentiation induced by nordihydroguaiaretic acid (NDGA). Methods　Immunohistochemistry (IHC) and in situ hybridization were used to detect the expression changes of GFAP protein and GFAP mRNA qualitatively and quantitatively. Results　The expression levels of GFAP protein and GFAP mRNA in NDGA treatment group were significantly increased compared with the control group (P<0.01). Conclusion　NDGA could induce GFAP gene in malignant glioma cells and the up-regulation of this gene expression might be one of the mechanisms by which NDGA induces glioma differentiation.

Objective　To explore the relationship between morphologic evolution and proliferative activity during hepatocarcinogenesis in rats. Methods　Imaging analysis technique was used to detect the morphologic parameters of cells in hepatic lesions in both Solt-Farber model and diethylnitrosamine (DEN)-induced liver cancer model. Immunohistochemistry was employed to detect proliferating cell nuclear antigen (PCNA) and bromodeoxyuridine (BrdU). Results　The oval cells were identified as irregular small proliferating cells in size of one-eighth of and with a nucleus/cytoplasm ratio of 6 times of the normal hepatocyte by image analysis. The morphometric parameters of basophil hepatocyte in precancerous foci and nodule were similar to those of the liver cancer cell. PCNA and BrdU positive cells were mainly localized within the proliferative foci and hepatocellular carcinoma (HCC) tissues. There was a better consistency between the development of hepatic lesions and cellular proliferative activity. Conclusion　The morphologic evolution is closely related to proliferative activity during hepatocarcinogenesis in rats.

Objective　To study the expressions of oncogenes c-Ha-ras, c-ki-ras, pan-ras and c-myc and point mutation of c-Ha-ras1 during hepatocarcinogenesis in rats. Methods　Immunohistochemistry, in situ hybridization and microdissection of tissue (MDT)-PCR-SSCP were used to detect the oncogene expressions and point mutation of c-Ha-ras1 in both Solt-Farber model and DEN-induced liver cancer model. Results　The overexpression of c-Ha-ras was closely associated with the formation and proliferation of the precancerous basophilic hepatocyte foci, while that of c-myc with the growth of the oval cell foci. The abnormalities of IGF-Ⅱ played an important role in the evolution of precancerous foci/nodules towards hepatocellular carcinoma (HCC). The overexpression of fms was only associated with HCC of some rats. Conclusion　Hepatocarcinogenesis in rats was related with the overexpression of c-Ha-ras, c-myc, IGF-Ⅱand fms and the point mutation of c-Ha-ras1, and overexpression of these oncogenes was associated with morphological evolution.

OBJECTIVETo explore effects of nordy on biological behaviors of human malignant glioblastoma cell line U87MG in vitro and transplanted tumor in vivo, and to identify the differential proteome upon Nordy induced differentiation.

METHODSGlioblastoma U87MG cells were induced to differentiate by synthetic lipoxygenase inhibitor, Nordy. The drug was also given via peritoneal injection to nude mice (27 mg/kg body weight) bearing orthotopic transplanted tumors of U87MG cells in the brain. The tumor volumes and GFAP expression were measured. Total proteins of U87MG cells after Nordy treatment were analysed by two-dimensional gel electrophoresis. PDQuest 7.1 computer software was used to compare protein profiles of the treated cells with that of untreated control. Differentially expressed proteins were then selected and characterized by matrix assisted laser desorption ionization-time of flight-mass spectrometry. The functional aspects of these proteins were analyzed by bioinformatics.

RESULTSNordy suppressed both the proliferation of U87MG cells in vitro and the tumor growth of orthotopic transplanted tumors in vivo (P < 0.01). The differentially expressed proteins induced by Nordy included proliferation-associated gene A, alternative splicing factor ASF-3, eukaryotic translation initiation factor 5A, coffilin 1 (non-muscle), beta galactoside binding lectin, glyceraldehyde-3-phosphate dehydrogenase, enolase 1 and an unknown protein.

CONCLUSIONSNordy promotes the differentiation of glioblastoma cells, by which it may serve as a therapeutic agent. Various proteins identified during Nordy-induced differentiation are involved in the cell proliferation, metabolism, differentiation, apoptosis and gene transcription.

Animals ; Antineoplastic Agents ; pharmacology ; Brain Neoplasms ; metabolism ; pathology ; Cell Differentiation ; Cell Line, Tumor ; Cell Proliferation ; Female ; Gene Expression Regulation, Neoplastic ; Glial Fibrillary Acidic Protein ; metabolism ; Glioblastoma ; metabolism ; pathology ; Humans ; Lipoxygenase Inhibitors ; pharmacology ; Male ; Masoprocol ; analogs & derivatives ; pharmacology ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; Neoplasm Transplantation ; Protein Array Analysis ; Proteome ; genetics ; metabolism ; Proteomics ; methods ; Random Allocation ; Tumor Burden

This study is to investigate whether the synthesized chiral compound Nordy has influence on the function of endothelial progenitor cells (EPCs) from human umbilical cord blood induced by vascular endothelial growth factor (VEGF). EPCs were isolated from human umbilical cord blood by density gradient centrifugation. After cultured for 7 -10 days, EPCs were prepared for detecting effect of Nordy on proliferation, migration and tubule-forming activity in Matrigel induced by VEGF. Incubation of EPCs with 100 micromol L(-1) Nordy for 24 h initially inhibited the proliferative capacity of EPCs induced by VEGF (P <0.05). Moreover, 25 -50 micromol L(-1) Nordy also exhibited inhibitory effect at 48 -72 h. In addition, 25 - 100 micromol L(-1) Nordy impaired EPCs migratory and tubule-forming capacity in vitro (P < 0.05). Nordy could inhibit in EPCs the functions of proliferation, migration and tubulogenesis induced by VEGF in vitro, which might be a possible mechanism of its anti-EPCs effects.
Antineoplastic Agents ; pharmacology ; Cell Movement ; drug effects ; Cell Proliferation ; drug effects ; Cells, Cultured ; Endothelial Cells ; cytology ; Fetal Blood ; cytology ; Humans ; Masoprocol ; analogs & derivatives ; pharmacology ; Neovascularization, Physiologic ; drug effects ; Stem Cells ; cytology ; Vascular Endothelial Growth Factor A ; antagonists & inhibitors