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Biomedical subjects

Ge Li

Publications and source records attributed to Ge Li.

At least 55 records · Page 3Linked to original sources
PubMed2004

Gabexate mesilate inhibits colon cancer growth, invasion, and metastasis by reducing matrix metalloproteinases and angiogenesis.

Gabexate mesilate (GM), a synthetic protease inhibitor, has an antiproteinase activity on various types of plasma serine proteases. However, its role on matrix metalloproteinases (MMPs) has not been identified. In this study, we investigated the effect of GM on MMPs and on the invasion and metastasis of human colon cancer cell lines and neoangiogenesis. The activities of MMPs secreted from these cells were significantly reduced by GM but unaffected by the serine protease inhibitor aprotinin. GM directly inhibited purified progelatinase A derived from T98G human glioblastoma cells. In vitro, GM significantly reduced the invasive ability of colon cancer cells but not cellular motility, whereas aprotinin affected neither. Liver metastatic ability and tumorigenic potential in nude mice were remarkably reduced on treatment with GM. Immunohistochemical analysis of GM-treated tumors in mice showed a marked increase in apoptosis and a significant reduction in tumor angiogenesis. Human umbilical vein endothelial cell proliferation, tube formation, and neoangiogenesis in the rabbit cornea and Matrigel implanted in mice were significantly inhibited by GM. These results suggest that GM is a novel inhibitor of MMPs and that it may inhibit the invasion and metastasis of human colon cancer cells by blocking MMPs and neoangiogenesis.

Animals↗
PubMed2004

Sequence variants of toll-like receptor 4 are associated with prostate cancer risk: results from the CAncer Prostate in Sweden Study.

Inflammation has been implicated as an etiological factor in several human cancers. Growing evidence suggests that chronic inflammation may also play a role in the etiology of prostate cancer. Considering that genetic susceptibility is a major risk factor for this disease, we hypothesize that sequence variants in genes that regulate inflammation may modify individual susceptibility to prostate cancer. The lipopolysaccharide receptor Toll-like receptor 4 (TLR4) is a central player in the signaling pathways of the innate immune response to infection by Gram-negative bacteria and is an important candidate inflammatory gene. We performed a systematic genetic analysis of TLR4 sequence variants by evaluating eight single-nucleotide polymorphisms that span the entire gene among 1383 newly diagnosed prostate cancer patients and 780 age- and residence-matched controls in Sweden. We found an association between a sequence variant (11381G/C) in the 3'-untranslated region of the TLR4 gene and prostate cancer risk. The frequency of the variant genotypes (CG or CC) was significantly higher in the patients (24.1%) than in the controls (19.7%; P = 0.02). The frequency of risk genotypes among patients diagnosed before the age of 65 years was even higher (26.3%). Compared with men who had the wild-type genotype of this single-nucleotide polymorphism (GG), those with GC or CC genotypes had a 26% increased risk for prostate cancer (odds ratio, 1.26; 95% confidence interval, 1.01-1.57) and 39% increased risk increased risk for early onset prostate cancer (before age 65 years; odds ratio, 1.39; 95% confidence interval, 1.02-1.91). The risk attributable to this variant for prostate cancer in Sweden was estimated to be 4.9%. Although the biological mechanism of the observed association remains to be elucidated, our finding supports a role for a bacteria-associated response pathway, possibly acting via inflammation, in the development of prostate cancer.

3' Untranslated Regions↗
PubMed2004

A polymorphism in the CDKN1B gene is associated with increased risk of hereditary prostate cancer.

The loss of cell cycle control is believed to be an important mechanism in the promotion of carcinogenesis. CDKN1B (p27) belongs to the Cip/Kip family and functions as an important cell cycle gatekeeper. Several lines of evidence from clinical studies and laboratory experiments demonstrate that CDKN1B is an important tumor suppressor gene in prostate cancer etiology. In addition, a case-control study has shown that the 326T/G (V109G) polymorphism in CDKN1B is associated with advanced prostate cancer. In light of the evidence for linkage between the chromosomal location of the CDKN1B gene (12p13) and prostate cancer susceptibility in several hereditary prostate cancer (HPC) populations, we hypothesized that sequence variants of CDKN1B play a role in HPC. To test this hypothesis, we first resequenced this gene in 96 HPC probands to identify germ-line mutations and sequence variants. We then genotyped the identified sequence variants among all family members of 188 HPC families and tested for their cosegregation with prostate cancer. In total, 10 sequence variants were identified, including three nonsynonymous changes. A family-based test, which is free from the effects of population stratification, revealed a significant association between single nucleotide polymorphism (SNP) -79C/T and prostate cancer (with a nominal P of 0.0005). The C allele of -79C/T was overtransmitted from parents to their affected offspring. Evidence for this association was primarily contributed by affected offspring whose age at diagnosis was <65 years. Together with the previous association study in a sporadic prostate cancer population, our new findings additionally suggest that germ-line variants of this gene play a role in prostate cancer susceptibility.

Aged↗
PubMed2004

Differential regulation of vimentin mRNA by 12-O-tetradecanoylphorbol 13-acetate and all-trans-retinoic acid correlates with motility of Hep 3B human hepatocellular carcinoma cells.

Vimentin is a growth-related gene and often expressed when epithelial cells are stimulated to proliferate by growth factors. In cancer, vimentin expression is associated with a dedifferentiated malignant phenotype, increased motility, invasive ability and poor prognosis. We studied the regulation of vimentin mRNA and multistep invasion processes following treatment of 12-O-tetradecanoylphorbol 13-acetate (TPA) and all-trans-retinoic acid (RA) in Hep 3B hepatocellular carcinoma cells. TPA showed marked induction of vimentin mRNA, while RA decreased the mRNA level. TPA or RA did not affect cell proliferation, cell-matrix protein adhesion, and matrix metalloproteinases and urokinase plasminogen activator activities. In vitro invasion ability was significantly increased or decreased with TPA or RA treatment, paralleled to the in vitro motile activity, respectively. These findings suggest that TPA and RA could modulate the invasive potential of Hep 3B cells by altering cellular motility related to differential regulation of vimentin mRNA.

Carcinoma, Hepatocellular↗
PubMed2004

Expression and regulation of interleukin-23 subunits in human peripheral blood mononuclear cells and hematopoietic cell lines in response to various inducers.

IL-23 is a novel cytokine composed of an IL-12 p40 and a p19 subunit. We analyzed human peripheral blood mononuclear cells (PBMC) and hematopoietic cell lines for constitutive expression of IL-23 and IL-12 subunits and expression following exposure to various stimuli, and investigated the mechanisms of their induction by LPS and SAC. IL-23 p19 and IL-12 p35 mRNAs were expressed in fresh PBMC, and expression of all IL-23 and IL-12 subunits was up-regulated by LPS and SAC. LPS-induced increase of IL-23 and IL-12 subunits expression was CD14-dependent, while CD14 was not involved in SAC-induced p19 transcription. Both LPS- and SAC-induced subunits expression required p38 MAPK pathway. PHA effected an increase of p19 mRNA in both CD4+ and CD8+ T cells, whereas p35 was minimally regulated by PHA. IFN-gamma primed monocytes for LPS stimulation of p19, p35 and p40 expression. p19 mRNA was detectable in most hematopoietic cell lines tested but p35 distribution was more restricted. A phorbol diester enhanced p19, p35 and p40 expression in EBV-positive cell lines. Our results suggest that both the subunits of IL-23 are tightly regulated; the expression pattern and regulation mode of IL-23 p19 is similar to as well as distinct from that of IL-12 p35.

Cell Line↗
PubMed2004

Expression of P2X7 in human hematopoietic cell lines and leukemia patients.

The P2X7 nucleotide receptor is an adenosine 5'-triphosphate (ATP) -gated ion channel, which is widely expressed in cells of hematopoietic origin and functions as a non-selective cation channel permeable to Na+, Ca2+, etc upon stimulation. Here, we investigated P2X7 expression in 11 human hematopoietic cell lines, representing different lineages, as well as bone marrow mononuclear cells (BMMC) samples from 87 leukemia and 10 myelodysplastic syndrome (MDS) patients. Semi-quantitative reverse transcription polymerase chain reaction (RT-PCR) and flow cytometry results showed that both P2X7 mRNA and protein were detected in eight cell lines with a non-lineage-specific manner. Samples from 69 leukemia and 9 MDS patients were P2X7 positive at mRNA level. Moreover, both positive rates and relative expression levels were significantly higher in acute myelogenous leukemia (AML), acute lymphoblastic leukemia (ALL), chronic myelogenous leukemia (CML), and MDS groups than that in normal donor group. The expression levels varied among AML subtypes with higher levels being observed in M4, M5, and M6 groups but not in M1 or M2 group. Furthermore, after one course of standard induction therapies, the remission rate in high P2X7 expression group was lower than that in either P2X7 negative group or low P2X7 expression group. Cytoplasmic free calcium increase was detected in five of eight P2X7+ cell lines as well as P2X7+ normal donor and patient samples tested, but not in three Epstein-Barr virus (EBV) positive cell lines (J6-1, Namalwa, and LCL-H) in Locke's solution upon stimulation by extracellular ATP or the more potent and specific agonist, 2',3'-O-(4-benzoyl)benzoyl-ATP (BzATP). The possible mechanisms causing the loss of P2X7 function were discussed.

Adolescent↗
PubMed2004

Expression of bioactive recombinant GSLL-39, a variant of human antimicrobial peptide LL-37, in Escherichia coli.

The human cationic antimicrobial peptide hCAP-18/LL-37 is the unique cathelicidin identified in human to date. It has broad spectrum of antimicrobial activities and LPS-neutralizing activity and is involved in angiogenesis. Both purified and synthetic LL-37 or its derivatives were used in the study on LL-37. However, production of LL-37 in Escherichia coli has not been established. In this study, its precursor instead of the mature peptide was adopted for expression to avoid the lethal effect of recombinant LL-37 on host cells. A thrombin recognition site was introduced between the cathelin-like domain and LL-37 domain by overlap PCR to construct fragment encoding modified precursor (mhCAP-18) to facilitate the final release of the recombinant peptide. Then mhCAP-18 was fused in-frame to thioredoxin gene under the control of inducible T7 promoter to construct expression vector pET-mhCAP-18. The soluble form fusion protein was expressed in E. coli and purified by Chelating Sepharose column chromatography. Thrombin digestion of the fusion protein yielded recombinant GSLL-39, which was then purified by cation-exchange chromatography. Recombinant GSLL-39, which has two extra residues on its N-terminus when compared with its native counterpart, showed similar antimicrobial activities against both Gram-negative and Gram-positive bacteria.

Antimicrobial Cationic Peptides↗
PubMed2004

IL-18 increases invasiveness of HL-60 myeloid leukemia cells: up-regulation of matrix metalloproteinases-9 (MMP-9) expression.

Similar to matrix metalloproteinases (MMP-9/-2), IL-18 was overexpressed in some hematologic malignancies such as acute myeloid leukemia (AML), which is associated with a poor clinical outcome. To establish a possible functional relationship between IL-18 and MMPs in myeloid leukemia, we used semi-quantitative PCR and zymographic analysis to examine whether IL-18 stimulates human myeloid leukemia cell line HL-60 to produce MMPs and/or specific tissue inhibitors (TIMPs), and to degrade extracellular matrix (ECM) gel in vitro. In the ECM invasion assay IL-18 significantly up-regulated transmigration of HL-60 cells, which in turn was inhibited by a synthetic MMP inhibitor: O-phenanthroline (o-PE), anti-MMP-9, anti-MMP-2 as well as anti-IL-18 monoclonal antibody (McAb), respectively, suggesting that induction of gelatinases by IL-18 leads to ECM degradation by these cells. Moreover, IL-18 could significantly increase MMP-9 but not MMP-2 production at both mRNA and/or protein level, slightly up-regulate TIMP-1 mRNA, and clearly induce TIMP-2 mRNA secretion. We postulate that IL-18 may in part play a role in the clinical aggressiveness of human myeloid leukemia by stimulating MMP-9 production.

Antibodies, Monoclonal↗
PubMed2004

Experimental study on the prevention and treatment of murine cytomegalovirus hepatitis by using allitridin.

Allitridin (diallyl trisulfide), a main effective compound of Allium sativum (garlic), was previously shown to inhibit the expression of immediate-early antigens and viral proliferation of human cytomegalovirus (HCMV) in vitro. Here we have examined the prophylactic and therapeutic efficacy of allitridin in a non-lethal murine cytomegalovirus (MCMV) hepatitis in methylprednisolone-immunosuppressed BALB/c mice. Allitridin was administered at 25mg/kg per day (equal to the mean human dose) and 75 mg/kg per day in two regimens: prophylaxis plus therapy beginning at 2 days before infection and lasting for 18 days, and therapy lasting for 14 days initiated at 2 days after infection. Ganciclovir (GCV)-treated, infected, and non-infected mice served as controls. MCMV DNA load in the liver, plasma alanine aminotransferase (ALT) level and Knodell's histological activity index (HAI) score of liver section were evaluated. We found that MCMV DNA load was significantly decreased in all allitridin- and GCV-treated mice, compared with infected controls. Concomitantly, histopathological lesions in the liver and plasma ALT levels were reduced. Statistically, no significant differences were detected between the combined allitridin prophylaxis plus therapeutic and therapeutic groups regardless of dose and the GCV groups. Our results demonstrate the therapeutic efficacy of allitridin in mouse models with MCMV hepatitis.

Allyl Compounds↗
PubMed2004

Membrane-bound macrophage colony-stimulating factor mediated auto-juxtacrine downregulates matrix metalloproteinase-9 release on J6-1 leukemic cell.

Earlier studies indicate that J6-1 human leukemic cells proliferate and propagate via the membrane-bound macrophage colony-stimulating factor (M-CSF)-mediated auto-juxtacrine mechanism. Matrix metalloproteinases (MMPs) can modulate the activity of cell membrane molecules and influence many cellular behaviors. Therefore, we hypothesized that MMP may also be involved in the membrane-bound M-CSF-mediated juxtacrine mechanism. First, we investigated whether blocking of membrane-bound M-CSF by neutralizing antibody to M-CSF or M-CSF receptor and adding of exogenous M-CSF are able to influence MMP-9 release. Next, we determined whether MMP-9 participated in J6-1 cells proliferation and influence the shedding of membrane-bound M-CSF and its receptor. Current studies show that blockade of the interaction between membrane-bound M-CSF and M-CSF receptor by antibody to M-CSF or M-CSF receptor promotes MMP-9 release. Moreover, we demonstrated that because of M-CSF mediated juxtacrine, lack of MMP-9 promotes J6-1 cell proliferation, in which a decrease in the shedding of cell-surface M-CSFR is involved. Hence, we suggest that membrane-bound M-CSF inhibit MMP-9 release and down-regulated MMP-9 contribute to juxtacrine stimulating in leukemic cell growth.

Base Sequence↗
PubMed2004

Transfection of mEpo gene to intestinal epithelium in vivo mediated by oral delivery of chitosan-DNA nanoparticles.

AIM: To prepare the chitosan-pmEpo nanoparticles and to study their ability for transcellular and paracellular transport across intestinal epithelia by oral administration. METHODS: ICR mice were fed with recombinant plasmid AAV-tetO-CMV-mEpo (containing mEpo gene) or pCMVbeta(containing LacZ gene), whether it was wrapped by chitosan or no. Its size and shape were observed by transmission electron microscopy. Agarose gel electrophoresis was used to assess the efficiency of encapsulation and stability against nuclease digestion. Before and after oral treatmant, blood samples were collected by retro-orbital puncture, and hematocrits were used to show the physiological effect of mEpo. RESULTS: Chitosan was able to successfully wrap the plasmid and to protect it from DNase degradation. Transmission electron microscopy showed that freshly prepared particles were approximately 70-150 nm in size and fairly spherical. Three days after fed the chitosan-pCMVbeta complex was fed, the mice were killed and most of the stomach and 30% of the small intestine were stained. Hematocrit was not modified in naive and 'naked' mEpo-fed mice, a rapid increase of hematocrit was observed during the first 4 days of treatment in chitosan-mEpo-fed animals, reaching 60.9+/-1.2% (P<0.01), and sustained for a week. The second feed (6 days after the first feed) was still able to promote a second hematocrit increase in chitosan-mEpo-fed animals, reaching 65.9+/-1.4% (P<0.01), while the second hematocrit increase did not appear in the 'naked' mEpo-second-fed mice. CONCLUSION: Oral chitosan-DNA nanoparticles can efficiently deliver genes to enterocytes, and may be used as a useful tool for gene transfer.

Administration, Oral↗
PubMed2004

[Determination of elements of hypericum perforatum L. in Xinjiang by microwave digestion-ICP-AES].

Sample digestion by microwave is of some merits: simple, rapid, saving agents, nonpollution and being easy digested. HNO3-HClO4 (5:1) was used as a microwave digestion agent. A direct method is reported for the determination of Fe, Ca, Mg, Zn, Mn, Cu, Na, K, Ba, Al, Pb and Cr in Hypericum perforatum L. in Xinjiang by inductively coupled plasma atomic emission spectrometry(ICP-AES). The selection of digestion conditions of the technique is described. The recoveries for these elements were 93.2%-103.0%, and the relative standard deviation (RSD) of the twelve samples were 0.4%-2.9%. According to standard sample GBW07602 bush twigs and leaves, the authors checked the method for accuracy and precision. The results were found to be basically consistent with the reference values. It was proved that the method features satisfactory precision and accuracy. The method was applied to the determination of plant materials with good agreement.

Aluminum↗
PubMed2003

[The clinical characteristics and its relationship with metabolic syndrome in elderly subjects with impaired glucose regulation].

OBJECTIVE: To study the clinical characteristics of impaired glucose regulation (IGR) in elderly subjects and its relationship with metabolic syndrome (MS). METHODS: The exploration of IGR in 2 810 Chongqing citizens over 40 years old was done by OGTT in a cross-section study. Normal glucose tolerance (NGT), IGR and diabetes (DM) were grouped based on the1999 diagnosis standard of WHO. IGR was composed of impaired fasting glucose (IFG), impaired glucose tolerance (IGT) and both of which. RESULTS: The prevalence of IGR was 18.11%, among which IGT (85.27%). Compared with the NGT group, the IGR group had higher age, body mass index (BMI), blood pressure, triglyceride (TG), total cholesterol (TC), low density lipoprotein cholesterol (LDL-c) and HOMA-IR, lower high density lipoprotein cholesterol (HDL-c) and HOMA-B. The IGR group had lower blood pressure, TG and HOMA-IR, and higher HOMA-B than the DM group. When each subgroup of IGR was compared with each other, both IFG plus IGT subgroup and IFG subgroup had higher BMI and HOMA-IR, and lower HOMA-B than IGT subgroup. The prevalences of hypertension, lipid disorder, obesity/overweight, and microalbuminuria in each subgroup of IGR were statistically higher than that of the NGT group. The prevalence of MS in the IFG plus IGT subgroup was higher than that of the IGT subgroup. CONCLUSIONS: The incidence of IGR was high in elderly people over 40 years old in local district of Chongqing city. There were various metabolic disorders in the subgroups of IGR. The IFG plus IGT and IFG group had higher BMI, hypertension, microalbuminuria and HOMA-IR, but lower HOMA-B than the IGT group.

Aged↗
PubMed2003

Expression of IL-18 and its receptor in human leukemia cells.

The importance of IL-18, although clearly established in solid tumors, has not been fully elucidated in human hematopoietic neoplasms. Here we examined the mRNA and protein for IL-18 in eight human hematopoietic cell lines representing different lineages and neoplasms including leukemia, lymphoma and others. Our results revealed that IL-18 mRNA was expressed in these cells and that the corresponding protein was found in the cytoplasm. Seven of eight cell lines were also found to express two subunits of the IL-18 receptor (IL-18R) at varied levels. Furthermore, 29 out of 51 leukemia patients tested were observed to express IL-18R with 18/29 (62%) co-expression of both receptor and ligand. By blocking the IL-18 loop using specific antisense oligodeoxynucleotide (ASON) for IL-18 mRNA or anti-human IL-18R monoclonal antibody (McAbR), we were not able to demonstrate a marked inhibition on the most leukemic cell lines growth. Moreover, the potential proliferation in vitro of primary AML cells co-expressing IL-18 and its receptor was not significantly enhanced by recombinant human IL-18, suggesting that IL-18 is not apparently implicated in the proliferation of the leukemia cells via an autocrine loop. Additionally, we also found the effective modulating effect of M-CSF, IFN-alpha and TNF-alpha on IL-18R expression, implying an important in vivo effect of cytokines on IL-18-induced reaction. Moreover, the modulation of IL-18R expression was possibly irrelevant to IFN-gamma secretion induced by these cytokines.

Adolescent↗
PubMed2003

Expression of LL-37/hCAP-18 gene in human leukemia cells.

LL-37/hCAP-18 is an important part of host defense. Several diseases in human are characterized by impairment in the function of LL-37/hCAP-18 peptide. We examined the expression of LL-37/hCAP-18 in a panel of hematopoietic cell lines representing multiple cell lineages. LL-37/hCAP-18 expression at mRNA level was detected and varied among six of nine cell lines. The level of Raji cells was about eight folds higher than that of Ramos cells. However, only two cell lines, J6-1 and U937, expressed protein products. We also investigated LL-37/hCAP-18 protein in nine leukemia and three idiopathic thrombocytopenic purpura (ITP) patients via immunocytochemical staining. The rate of LL-37/hCAP-18 positive cells ranged from 60 (ITP) to 0.5% (M5). These data suggested that the low translation efficiency of LL-37/hCAP-18 expresses in some leukemia cells might be one of the reasons that leukemia patients were susceptible to infection.

Adult↗
PubMed2003

[Morphological changes of tissues after extensive soft tissue injury].

OBJECTIVE: To study the pathological morphological changes for diagnosing the cause of death of extensive soft tissue injury or crush syndrome. METHODS: The tissues were stained by HE and IHC. RESULTS: (1) The Mb positive rate was 60%, 75%, 95% respectively. (2) Both the HSP70 positive rate of hearts and brains were 90%. CONCLUSION: (1) The animal model of broad soft tissue injury was established. (2) Accumulated the pathological morphological data for diagnosing the cause of death of extensive soft tissue injury or crush syndrome.

Animals↗
PubMed2003

Expression and significance of IL-18 in the bone marrow of patients with hematological diseases.

OBJECTIVE: To investigate the levels of IL-18 in the bone marrow of both normal subjects and patients with hematological diseases and to determine the possible significance of IL-18 in pathogenesis of some hematological malignancies. METHODS: The IL-18 mRNA levels in the bone marrow of 140 patients with hematological diseases and 15 normal donors were determined by the semi-quantitative reverse transcriptase polymerase chain reaction (RT-PCR). Immunohistochemical method was used to detect IL-18 protein in 12 patients with acute myeloid leukemia (AML). The possible regulation of IL-18 for proliferation of some leukemia cells was investigated using antisense techniques. RESULTS: IL-18 mRNA levels were obviously higher in the patients with leukemia or other malignant hematological diseases (OMHD) than in normal donors. However, no significant difference was found in the level of transcription between patients with iron deficiency anemia (IDA) and normal controls. Immunohistochemical method confirmed the presence of IL-18 protein in 10 out of 12 AML cases with positive transcription. By 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay, IL-18 antisense oligodeoxynucleotides (ASON) clearly inhibited the growth of J6-1 and HL-60 cells (42% and 12% inhibited, respectively) in a dose-dependent manner. CONCLUSIONS: IL-18 was detected at elevated levels in the bone marrow of patients with some hematological malignancies, and might be involved in the proliferation of certain leukemic cells in vivo through an autocrine mechanism.

Adolescent↗