Biomedical subjects

Li-Ping Song

Publications and source records attributed to Li-Ping Song.

9 recordsLinked to original sources

PubMed2006

Hypoxia inducible factor-1alpha and leukemic cell differentiation.

Arsenic trioxide (As2O3, ATO) is a recently developed drug for the effective treatment of acute promyelocytic leukemia (APL). Experimental studies showed that in vitro differentiation-inducing ability on APL cells of this drug is not significant compared with its in vivo activity. We unexpectedly found recently that hypoxia-mimetic agents and moderate real hypoxia triggered acute myeloid leukemic cells to undergo differentiation. Furthermore, intermittent hypoxia significantly prolonged the survival of the transplanted leukemic mice with inhibition of infiltration and induction of differentiation of leukemic cells. In the following works, molecular mechanisms of hypoxia-induced differentiation were investigated and some interesting results have been obtained. This review will shortly summarize the related progresses and discuss the questions remained to be further investigated.

Animals↗

PubMed2006

Comparative proteomic analysis of hypoxia-treated and untreated human leukemic U937 cells.

We reported recently that moderate hypoxia and hypoxia-mimetic agents could induce growth arrest and differentiation of leukemic cells via the mediation of hypoxia-inducible factor 1 alpha (HIF-1alpha), but the exact molecular mechanisms remain largely unknown. In this study, human acute promonocytic leukemic U937 cells were incubated under 2% O2 or in 50 microM of the hypoxia mimetic agent cobalt chloride (CoCl2) and normal oxygen for 24 h, and their protein expression profiles were compared by 2-DE coupled with MALDI-TOF/TOF MS/MS. We identified 62 and 16 proteins that were significantly deregulated by hypoxia and CoCl2 treatment, respectively. These proteins were mainly involved in metabolism, gene expression regulation, signal transduction, cell proliferation, differentiation and apoptosis. As an example, N-myc downstream regulated gene 1 (NDRG1), a putative differentiation-related gene, was up-regulated in both 2% O2- and CoCl2-treated U937 cells. Moreover, enforced HIF-1alpha expression also elevated NDRG1 mRNA and protein in U937 cells. These data will provide some clues for understanding mechanisms by which leukemic cells response to hypoxia.

Apoptosis↗

PubMed2006

[Cellular uptake and cytotoxicity of modified chitosans as gene carriers].

OBJECTIVE: To evaluate the effects of arginine modified chitosan or hexadecylated modified chitosan as gene carriers on the cellular uptake by vascular smooth muscle cells and its in vitro cytotoxicity. METHODS Plasmid DNA was labeled with alpha-32P-dATP and complexed with the modified chitosans or unmodified chitosan to form nanoparticle complexes by complex coacervation method. Uptake of all kinds of chitosan/ DNA nanoparticle complexes (CNC) by A10 cells was measured by beta-liquid scintillation counting. The in vitro cytotoxicity of the CNC was evaluated by the 3-[4,5-dimethylthiazol-2-yl]-2, 5-diphenyltetrazolium bromide (MTT) assay. RESULTS: The diameters of the CNC ranged from 55.9-174.9 nm and the zeta potentials were from 10. 8 mV for the arginine modified chitosan/DNA nanoparticle complexes (ACNC) to 1.8 mV for the hexadecylated chitosan/DNA nanoparticle complexes (HCNC). The cellular uptake of the modified chitosan/ DNA nanoparticle complexes (MCNC) by A10 cells increased significantly when compared with the unmodified chitosan/DNA nanoparticle complexes (UCNC) (P < 0.05), with the HCNC at N/P ratio of 1:1 and the ACNC at ratio of 8:1 showing the highest cellular uptake (1.3 fold higher than UCNC, P < 0.05). MCNC were much less cytotoxic when compared with Lipofectamine 2000-DNA nanoparticles. CONCLUSION: DNA nanoparticle complexes prepared with either arginine or hexadecylated modified chitosan can improve the cellular uptake of the DNA, while the in vitro cytotoxicity of both of the modified chitosan is much less than that of Lipofectamine 2000.

Animals↗

PubMed2005

Apoptosis of pancreatic cancer BXPC-3 cells induced by indole-3-acetic acid in combination with horseradish peroxidase.

AIM: To explore the mechanisms underlying the apoptosis of human pancreatic cancer BXPC-3 cells induced by indole-3-acetic acid (IAA) in combination with horseradish peroxidase (HRP). METHODS: BXPC-3 cells derived from human pancreatic cancer were exposed to 40 or 80 micromol/L IAA and 1.2 microg/mL HRP at different times. Then, MTT assay was used to detect the cell proliferation. Flow cytometry was performed to analyze cell cycle. Terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling assay was used to detect apoptosis. 2,7-Dichlorofluorescin diacetate uptake was measured by confocal microscopy to determine free radicals. Level of malondialdehyde (MDA) and activity of superoxide dismutase (SOD) were measured by biochemical methods. RESULTS: IAA/HRP initiated growth inhibition of BXPC-3 cells in a dose- and time-dependent manner. Flow cytometry revealed that the cells treated for 48 h were arrested at G1/G0. After exposure to 80 micromol/L IAA plus 1.2 microg/mL HRP for 72 h, the apoptosis rate increased to 72.5 per thousand, which was nine times that of control. Content of MDA and activity of SOD increased respectively after treatment compared to control. Meanwhile, IAA/HRP stimulated the formation of free radicals. CONCLUSION: The combination of IAA and HRP can inhibit the growth of human pancreatic cancer BXPC-3 cells in vitro by inducing apoptosis.

Apoptosis↗

PubMed2005

[Effects of mitomycin C on the expression and transport of ice-nuclei proteins of Erwinia herbicola].

Abstract: In this paper, Mitomycin C (MMC) was added to different kinds of medium to study the effects of different cultural conditions on the Erwinia herbicola 10025A. For the first time it was confirmed that the expressed activity of the ice-nuclei active protein was different from its transportable manner from the ice nucleation active bacteria (Erwinia herbicola 10025A). The findings indicated that MMC could stimulate the SOS response,and induce the synthesis of some enzymes and proteins, which take part in repairing the damaged DNA. The effects of the MMC on the E. herbicola under different media were different. It could increase the ice nucleation activity of the E. herbicola, forming new small vesicles, which are secreted to the outside of membrane. The importance of this research for study the living mechanism of cells ander poor condition was discussed.

Bacterial Outer Membrane Proteins↗

PubMed2005

[Influence of water-soluble additives on drug release kinetics from biodegradable poly(lactic-co-glycolic acid) matrix].

AIM: To evaluate the effects of an array of additives on drug release from double-layered poly(lactic-co-glycolic acid) (PLGA) matrices. METHODS: Additives differing in molecular size, hydrophilicity and steric configuration were selected for this study. An anti-proliferative 2-aminochromone, U-86983 (U-86, Pharmacia and Upjohn), was used as a model agent because of our interest in investigating local drug delivery systems for the inhibition of restenosis. RESULTS: In vitro release of U-86 PLGA matrices without additive showed a typical biphasic release kinetics, i.e. a slow diffusion release (Phase I) followed by a fast erosion-mediated release (Phase II). The water-soluble additives in PLGA matrices changed the biphasic release pattern to a near monophasic profile by increasing the release of the Phase I. Increasing the ratio of additives to PLGA in matrices caused a significant increase in U-86 release rates. A high molecular weight water-soluble additive, Pluronic F127, resulted in a matrix showing perfect zero-order release kinetics. The morphologic evaluation of matrices using scanning electron microscopy indicated that the water-soluble additives were leachable and thus generated a highly porous structure in the matrices. Conclusion Water-solubility, molecular size and steric configuration of additives are the important determinants in generating various types of pore structures in polymer matrix which in turn affect the release mechanism and release kinetics.

Biocompatible Materials↗

PubMed2004

[Clinical study of 22 cases of primary gastrointestinal lymphoma].

BACKGROUND & OBJECTIVE: Primary gastrointestinal lymphoma (PGIL) is extranodal non-Hodgkin's lymphoma (NHL) that originates from extra-nodal tissue of gastrointestinal (GI) tract and has specific clinical and pathological features. This study was to report the clinical and pathological features as well as the treatment outcome of this disease. METHODS: The clinical data of 22 cases of PGIL admitted and treated from January 1994 to June 2000 in the First Hospital of Xi'an Jiaotong University were analyzed retrospectively. The diagnosis was confirmed histologically. RESULTS: All the patients were followed up for more than 3 years; among them 13 patients were followed up to 5 years. The 3-year and 5-year survival rates were 45.5% (10/22) and 38.5% (5/13), respectively. The survival rates decreased with the progression of the clinical stage. Low-grade marginal zone derived mucosa-associated lymphoid tissue lymphoma (MALT) showed a better prognosis than other pathological types. Of the 16 patients who received treatment attained complete remission (CR), the 3-year and 5-year survival rates were 62.5% (10/16) and 45.5% (5/11), respectively, whereas the 3-year and 5-year survival rates of the 6 non-controlled patients were 0 and 0. Among the twelve cases treated with surgery alone, the 3-year and 5-year survival rates were 33.3% (4/12) and 10% (1/10), respectively. For those receiving surgery combined with chemotherapy and radiotherapy (5 cases received adjuvant chemotherapy after surgery, and 1 patient received abdominal irradiation after the surgery), the 3-year and 5-year survival rates were 83.3% (5/6) and 66.7% (2/3), respectively. CONCLUSION: The prognosis of PGIL is related to control of the primary disease.

Adult↗

PubMed2003

A new model of trispecific antibody resulting the cytotoxicity directed against tumor cells.

Bispecific antibodies (BsAb) with specificity to both tumor cells and CD3 molecule were believed to be promising immunological tools for the therapy with minimal residual diseases by activating cytotoxic T cells. However, without costimulatory molecule CD28, the activated T cells tended to apoptosis. In order to kill tumor cells more efficiently, a recombinant multifunctional single-chain trispecific antibody (scTsAb), which contains anti-ovarian carcinoma (OC) scFv, anti-CD3 scFv and VH domain of anti-CD28 antibody, was constructed and expressed in E. coli BL21 Star strain. The scTsAb showed strong binding avidities to membrane antigen of SK-OV-3 cell, CD3 molecule on Jurkat cell, and recombinant CD28 antigen. It was further demonstrated that this scTsAb could activate peripheral blood T cells to elicit strong cytotoxicity against SK-OV-3 cells. This new type of recombinant scFv antibody set up a new technological platform for T cells based immunotherapy against cancer, especially with the failure on MHC antigen presentation or absence of costimulating signal.

Antibodies, Bispecific↗

PubMed2003

[Protein splicing and its application].

Protein splicing is a newly discovered posttranslational editing process that removes an internal protein fragment from the protein precursor. During the splicing process the internal protein fragment, intein, triggered the self-excision from the precursor protein and the concomitant ligation of the flanking protein fragments, exteins. The self-catalysis requires neither auxiliary enzymes nor cofactors and only involves four intramolecular reactions. A number of key catalytic residues in inteins and flanking fragments have been identified, which led to the development of the protein splicing process as a protein engineering tool. Controllable cleavage of the peptide bond at either the N or the C terminus of an intein has allowed the design of novel strategies for manipulation of protein and peptides. Affinity purification of recombinant proteins can be facilitated by fusion the target protein with an intein. The fusion also creates C-terminal thioester, which expands the scope of chemical ligation in protein. Inteins can be engineered in a "split and inverted" configuration to form a cyclic polypeptide consisting of the sequence linking two intein subdomains. This article summarizes the recent advance in the mechanism of protein splicing and its applications in protein purification, protein ligation and protein cyclization.

Inteins↗