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Cheng Li

Publications and source records attributed to Cheng Li.

At least 37 records · Page 2Linked to original sources
PubMed2005

Significance and relationship between infiltrating inflammatory cell and tumor angiogenesis in hepatocellular carcinoma tissues.

AIM: To investigate the relationship between infiltrating inflammatory cell and tumor angiogenesis in hepatocellular carcinoma (HCC) tissues and their clinicopathological features. METHODS: The paraffin-embedded specimens from 70 cases with HCC were stained using EliVision immunohistochemistry with mAbs against CD68, tryptase, and CD34. The counts of tumor-associated macrophage (TAM), mast cell (MC) and tumor microvessel (MV) were performed in the tissue sections. RESULTS: The mean counts of TAM, MC, and MV in HCC tissues were significantly higher than those in pericarcinomatous liver tissues (TAM: 69.31+/-11.58 vs 40.23+/-10.36; MC:16.74+/-5.67 vs 7.59+/-4.18; MV: 70.11+/-12.45 vs 38.52+/-11.16, P<0.01). The MV count in the patients with metastasis was markedly higher than that with non-metastasis (P<0.01). In addition, the MC count in the patients with poorly differentiated HCC was obviously higher than that with well differentiated HCC (P<0.01). The correlation analysis showed that the TAM count was significantly correlated with the count of MV (r=0.712, P<0.01), and the MC count was obviously correlated with the MV count (r=0.336, P<0.05). CONCLUSION: TAM and MC might be closely related to the enhancement of tumor angiogenesis. The MV count might be associated with tumor invasion and metastasis. Moreover, the MC count might be associated with tumor differentiation and prognosis of HCC.

Adult↗
PubMed2005

Novel pheochromocytoma susceptibility loci identified by integrative genomics.

Pheochromocytomas are catecholamine-secreting tumors that result from mutations of at least six different genes as components of distinct autosomal dominant disorders. However, there remain familial occurrences of pheochromocytoma without a known genetic defect. We describe here a familial pheochromocytoma syndrome consistent with digenic inheritance identified through a combination of global genomics strategies. Multipoint parametric linkage analysis revealed identical LOD scores of 2.97 for chromosome 2cen and 16p13 loci. A two-locus parametric linkage analysis produced maximum LOD score of 5.16 under a double recessive multiplicative model, suggesting that both loci are required to develop the disease. Allele-specific loss of heterozygosity (LOH) was detected only at the chromosome 2 locus in all tumors from this family, consistent with a tumor suppressor gene. Four additional pheochromocytomas with a similar genetic pattern were identified through transcription profiling and helped refine the chromosome 2 locus. High-density LOH mapping with single nucleotide polymorphism-based array identified a total of 18 of 62 pheochromocytomas with LOH within the chromosome 2 region, which further narrowed down the locus to <2 cM. This finding provides evidence for two novel susceptibility loci for pheochromocytoma and adds a recessive digenic trait to the increasingly broad genetic heterogeneity of these tumors. Similarly, complex traits may also be involved in other familial cancer syndromes.

Adrenal Gland Neoplasms↗
PubMed2005

Development of a high-throughput in vitro assay using a novel Caco-2/rat hepatocyte system for the prediction of oral plasma area under the concentration versus time curve (AUC) in rats.

INTRODUCTION: Previously, we have shown that a novel Caco-2/human hepatocyte system is a useful model for the prediction of oral bioavailability in humans. In this study, we attempted to use a similar system in a high-throughput screening mode for the selection of new compound entities (NCE) in drug discovery. METHODS: A total of 72 compounds randomly selected from three different chemotypes were dosed orally in rats. In vivo plasma area under the concentration versus time curve (AUC) from 0-6 h of the parent compound was determined. The same compounds were also tested in the Caco-2/rat hepatocyte system. In vitro AUC from 0-3 h in the Caco-2 rat hepatocyte system was determined. RESULTS: The predictive usefulness of the Caco-2/rat hepatocyte system was evaluated by comparing the in vivo plasma AUC and the in vitro AUC. Linear regression analysis showed a reasonable correlation (R2 = 0.5) between the in vivo AUC and the in vitro AUC. Using 0.4 microM h in vivo AUC as a cut-off, compounds were categorized as either low or high AUC. The in vitro AUC successfully matched the corresponding in vivo category for sixty-three out of seventy-two compounds. DISCUSSION: The results presented in this study suggest that the Caco-2/rat hepatocyte system may be used as a high-throughput screen in drug discovery for pharmacokinetic behaviors of compounds in rats.

Administration, Oral↗
PubMed2005

[Presurgical evaluation and surgical treatment of medically refractory epilepsy: a report of 162 cases].

OBJECTIVES: To study presurgical evaluation and surgical treatment of medically refractory epilepsy. METHODS: One hundred and sixty-two cases of refractory epilepsy were analysed by their clinical manifestation, neuroradiology and neuroelectrophysiology. Different operative techniques were performed to all the 162 cases according to those analyses. RESULTS: Total effective rate of the surgical treatment was 87.7% and most patients have better life than preoperation. CONCLUSION: Surgical treatment with accurate preoperative location of the epileptogenic zone and suitable operative techniques is an effective method in the treatment of refractory epilepsy.

Adolescent↗
PubMed2005

A HIF1alpha regulatory loop links hypoxia and mitochondrial signals in pheochromocytomas.

Pheochromocytomas are neural crest-derived tumors that arise from inherited or sporadic mutations in at least six independent genes. The proteins encoded by these multiple genes regulate distinct functions. We show here a functional link between tumors with VHL mutations and those with disruption of the genes encoding for succinate dehydrogenase (SDH) subunits B (SDHB) and D (SDHD). A transcription profile of reduced oxidoreductase is detected in all three of these tumor types, together with an angiogenesis/hypoxia profile typical of VHL dysfunction. The oxidoreductase defect, not previously detected in VHL-null tumors, is explained by suppression of the SDHB protein, a component of mitochondrial complex II. The decrease in SDHB is also noted in tumors with SDHD mutations. Gain-of-function and loss-of-function analyses show that the link between hypoxia signals (via VHL) and mitochondrial signals (via SDH) is mediated by HIF1alpha. These findings explain the shared features of pheochromocytomas with VHL and SDH mutations and suggest an additional mechanism for increased HIF1alpha activity in tumors.

Journal Article↗
PubMed2005

The RhoGAP protein DLC-1 functions as a metastasis suppressor in breast cancer cells.

The identification of molecular signatures characteristic of tumor cells that are capable of metastatic spread is required for the development of therapeutic interventions to abrogate this lethal process. To facilitate this, we have previously characterized an experimental system in which the role of candidate metastasis-related genes can be screened and tested. Monoclonal cell lines M4A4 and NM2C5 are spontaneously occurring sublines of the MDA-MB-435 cell breast tumor cell line that exhibit phenotypic differences in growth, invasion, and metastatic efficiency in athymic mice. In this study, transcriptional profiles of these cell lines were created using oligonucleotide microarrays representing over 12,000 genes. Intensity modeling and hierarchical clustering analysis identified a 171-gene expression signature that correlated with metastatic phenotype and highlighted several GTPase signaling components. Restoration of one of these GTPases, deleted in liver cancer-1 (DLC-1), in metastatic M4A4 cells to levels observed in the nonmetastatic NM2C5 cell line resulted in the inhibition of migration and invasion in vitro and a significant reduction in the ability of these cells to form pulmonary metastases in athymic mice. These studies show the utility of expression profiling, in an appropriate experimental system, to identify genetic determinants of metastatic sufficiency. The finding that DLC-1 can act as a metastasis-suppressor gene supports an influential role for GTPase signaling in tumor progression.

Animals↗
PubMed2005

Integrative genomic analyses identify MITF as a lineage survival oncogene amplified in malignant melanoma.

Systematic analyses of cancer genomes promise to unveil patterns of genetic alterations linked to the genesis and spread of human cancers. High-density single-nucleotide polymorphism (SNP) arrays enable detailed and genome-wide identification of both loss-of-heterozygosity events and copy-number alterations in cancer. Here, by integrating SNP array-based genetic maps with gene expression signatures derived from NCI60 cell lines, we identified the melanocyte master regulator MITF (microphthalmia-associated transcription factor) as the target of a novel melanoma amplification. We found that MITF amplification was more prevalent in metastatic disease and correlated with decreased overall patient survival. BRAF mutation and p16 inactivation accompanied MITF amplification in melanoma cell lines. Ectopic MITF expression in conjunction with the BRAF(V600E) mutant transformed primary human melanocytes, and thus MITF can function as a melanoma oncogene. Reduction of MITF activity sensitizes melanoma cells to chemotherapeutic agents. Targeting MITF in combination with BRAF or cyclin-dependent kinase inhibitors may offer a rational therapeutic avenue into melanoma, a highly chemotherapy-resistant neoplasm. Together, these data suggest that MITF represents a distinct class of 'lineage survival' or 'lineage addiction' oncogenes required for both tissue-specific cancer development and tumour progression.

Cell Line, Tumor↗
PubMed2005

Homozygous deletions and chromosome amplifications in human lung carcinomas revealed by single nucleotide polymorphism array analysis.

Genome-wide copy number changes were analyzed in 70 primary human lung carcinoma specimens and 31 cell lines derived from human lung carcinomas, with high-density arrays representing approximately 115,000 single nucleotide polymorphism loci. In addition to previously characterized loci, two regions of homozygous deletion were found, one near the PTPRD locus on chromosome segment 9p23 in four samples representing both small cell lung carcinoma (SCLC) and non-small cell lung carcinoma (NSCLC) and the second on chromosome segment 3q25 in one sample each of NSCLC and SCLC. High-level amplifications were identified within chromosome segment 8q12-13 in two SCLC specimens, 12p11 in two NSCLC specimens and 22q11 in four NSCLC specimens. Systematic copy number analysis of tyrosine kinase genes identified high-level amplification of EGFR in three NSCLC specimens, FGFR1 in two specimens and ERBB2 and MET in one specimen each. EGFR amplification was shown to be independent of kinase domain mutational status.

Carcinoma, Non-Small-Cell Lung↗
PubMed2005

Chromic-P32 phosphate treatment of implanted pancreatic carcinoma: mechanism involved.

AIM: To study the effects of chromic-P32 phosphate (32P colloids) interstitial administration in Pc-3 implanted pancreatic carcinoma, and investigate its anticancer mechanism. METHODS: Ninety-eight tumor bearing nude mice were killed at different time points after the injection of 32P colloids to the tumor core with observed radioactivity. The light microscopy, transmission electron microscopy (TEM) and immuno-histochemistry and flow cytometry were used to study the rates of tumor cell necrosis, proliferating cell nuclear antigen index, the micro vessel density (MVD). The changes of the biological response to the lymphatic transported 32P colloids in the inguinal lymph node (ILN) were dynamically observed, and the percentage of tumor cell apoptosis, and Apo2.7, caspase-3, Bcl-2, Bax-related gene expression were observed too. RESULTS: The half-life of effective medication is 13 d after injection of 32P colloids to the tumor stroma, in 1-6 groups, the tumor cell necrosis rates were 20%, 45%, 65%, 70%, 95% and 4%, respectively (F = 4.14-105.36, P<0.01). MVD were 38.5+/-4.0, 28.0+/-2.9, 17.0+/-2.9, 8.8+/-1.5, 5.7+/-2.3 and 65.0+/-5.2 (t = 11.9-26.1, P<0.01), respectively. Under TEM fairly differentiated Pc-3 cells were found. Thirty days after medication, tumors were shrunk and dried with scabs detached, and those in control group increased in size prominently with plenty of hypodermic blood vessels. In all animals the ILN were enlarged but in medicated animals they appeared later and smaller than those in control group. The extent of irradiative injury in ILN was positively correlated to the dosage of medication. Typical tumor cell apoptosis could be found under TEM in animals with intra-tumoral injection of low dosed 32P colloids. The peak of apoptosis occurred in 2.96 MBq group and 24 h after irradiation. In the course of irradiation-induced apoptosis, the value of Bcl-2/Bax was down regulated; Apo2.7 and caspase-3 protein expression were prominently increased dose dependently. CONCLUSION: 32P colloids intra-tumor injection having prominent anticancer effectiveness may reveal the ability of promoting cell differentiation. The low dose 32P colloids may induce human pancreatic carcinoma Pc-3 implanted tumor cell apoptosis; Apo2.7, caspase-3, Bcl-2 and Bax protein participated in regulating the process of irradiation induced cell apoptosis.

Animals↗
PubMed2005

Comparative linkage analysis and visualization of high-density oligonucleotide SNP array data.

BACKGROUND: The identification of disease-associated genes using single nucleotide polymorphisms (SNPs) has been increasingly reported. In particular, the Affymetrix Mapping 10 K SNP microarray platform uses one PCR primer to amplify the DNA samples and determine the genotype of more than 10,000 SNPs in the human genome. This provides the opportunity for large scale, rapid and cost-effective genotyping assays for linkage analysis. However, the analysis of such datasets is nontrivial because of the large number of markers, and visualizing the linkage scores in the context of genome maps remains less automated using the current linkage analysis software packages. For example, the haplotyping results are commonly represented in the text format. RESULTS: Here we report the development of a novel software tool called CompareLinkage for automated formatting of the Affymetrix Mapping 10 K genotype data into the "Linkage" format and the subsequent analysis with multi-point linkage software programs such as Merlin and Allegro. The new software has the ability to visualize the results for all these programs in dChip in the context of genome annotations and cytoband information. In addition we implemented a variant of the Lander-Green algorithm in the dChipLinkage module of dChip software (V1.3) to perform parametric linkage analysis and haplotyping of SNP array data. These functions are integrated with the existing modules of dChip to visualize SNP genotype data together with LOD score curves. We have analyzed three families with recessive and dominant diseases using the new software programs and the comparison results are presented and discussed. CONCLUSIONS: The CompareLinkage and dChipLinkage software packages are freely available. They provide the visualization tools for high-density oligonucleotide SNP array data, as well as the automated functions for formatting SNP array data for the linkage analysis programs Merlin and Allegro and calling these programs for linkage analysis. The results can be visualized in dChip in the context of genes and cytobands. In addition, a variant of the Lander-Green algorithm is provided that allows parametric linkage analysis and haplotyping.

Family Health↗
PubMed2005

Ovarian cancer is a heterogeneous disease.

The purpose of this study was to systematically evaluate the molecular profiles of different histologic types of epithelial ovarian cancer before the disease has metastasized beyond the ovary. Stage 1 epithelial ovarian cancers were chosen for analysis of early genetic events associated with different cell types. Allelotyping of 47 cases was performed using 224 polymorphic markers. Analysis with Fisher's exact test found markers specific for grade 3 tumors and clear cell histology. Hierarchal clustering analysis using dChip software revealed that the pattern of allele loss in eight regions on four chromosomes led to grouping of grade 3 tumors, endometrioid (grades 1 and 2) tumors, and clear cell tumors. We conclude that ovarian cancer is a heterogeneous disease in which histologic phenotypes correlate with distinct genetic patterns.

Adenocarcinoma, Clear Cell↗
PubMed2005

Phylogeographic analysis of the Bufo gargarizans species complex: a revisit.

Using mtDNA sequencing and allozyme electrophoresis data, we tested the "vicariance followed by dispersal" hypothesis of the Bufo gargarizans species group and re-evaluated the species status in the general lineages species concept. A phylogenetic analysis suggested that dispersal, instead of vicariance, dominated the history of the species group. There was a general trend of west to east dispersal, while some lineages from the east subsequently returned to the west. The secondary admixture of those previously allopatric lineages produced substantial levels of sympatric genetic diversity, often as high as 7.0% pairwise difference within populations. The phylogenetic hypothesis does not support the current two species designation. Neither B. andrewsi nor B. gargarizans represents an independent evolutionary lineage, and monophyletic groups did not correspond to geographically discrete groups. Allozyme data also failed to reveal any fixed allelic difference among the populations. Therefore, we recommend regarding the complex as a single species, Bufo gargarizans, without subspecies division.

Animals↗
PubMed2005

In vitro and in vivo studies of ePTFE vascular grafts treated with P15 peptide.

The purpose of this study is to evaluate the effectiveness of P15 cell-binding peptide treated ePTFE vascular grafts in vitro and in vivo. The P15 peptide was covalently immobilized onto ePTFE vascular grafts by an atmospheric plasma coating method. In vitro cell growth properties were studied using primary human umbilical vein endothelial cells (HUVECs) and primary human umbilical artery smooth muscle cells (HUASMCs). X-ray photoelectron spectroscopy and amino-acid analysis were used to analyze the surface characteristics of the peptide treated and untreated grafts. The cell growth study showed that the P15 peptide effectively promoted the adhesion and proliferation of endothelial cells. 700% more endothelial cells were proliferated on the P15-treated ePTFE grafts compared to the untreated ePTFE controls. In contrast, the P15 peptide was significantly less effective for promoting the adhesion and proliferation of smooth muscle cells than endothelial cells; only about 100% more smooth muscle cells proliferated on the P15-treated samples compared to the untreated control samples. The sheep model was used in the in vivo study. The amount of neointimal hyperplasia present at the arterial and venous sides of the anastomosis and the degree of endothelialization on the luminal surface of the grafts were assessed. Four P15-treated grafts and two control grafts were implanted as arteriovenous grafts between the femoral artery and vein or the carotid artery and jugular vein in two sheep (n = 6). The in vivo study showed that the thickness of the neointimal hyperplasia of untreated grafts was 3-times thicker than that of P15-treated grafts (P < 0.05) at the venous side of the anastomosis. P15-treated grafts also had a higher degree of endothelialization on the graft lumen.

Animals↗
PubMed2005

Global gene expression profiling in whole-blood samples from individuals exposed to metal fumes.

Accumulating evidence demonstrates that particulate air pollutants can cause both pulmonary and airway inflammation. However, few data show that particulates can induce systemic inflammatory responses. We conducted an exploratory study using microarray techniques to analyze whole-blood total RNA in boilermakers before and after occupational exposure to metal fumes. A self-controlled study design was used to overcome the problems of larger between-individual variation interferences with observations of relatively smaller changes caused by environmental exposure. Moreover, we incorporated the dichotomous data of absolute gene expression status in the microarray analyses. Compared with nonexposed controls, we observed that genes with altered expression in response to particulate exposure were clustered in biologic processes related to inflammatory response, oxidative stress, intracellular signal transduction, cell cycle, and programmed cell death. In particular, the preinflammatory cytokine interleukin 8 and one of its receptors, chemokine receptor 4, seemed to play important roles in early-stage response to heavy metal exposure and were down-regulated. Furthermore, most observed expression variations were from nonsmoking exposed individuals, suggesting that smoking profoundly affects whole-blood expression profiles. Our study is the first to demonstrate that with a paired sampling study design of pre- and postexposed individuals, small changes in gene expression profiling can be measured in whole-blood total RNA from a population-based study. This technique can be applied to evaluate the host response to other forms of environmental exposures.

Adult↗
PubMed2005

Expression of heat shock proteins and heat shock protein messenger ribonucleic acid in human prostate carcinoma in vitro and in tumors in vivo.

Heat shock proteins (HSPs) are thought to play a role in the development of cancer and to modulate tumor response to cytotoxic therapy. In this study, we have examined the expression of hsf and HSP genes in normal human prostate epithelial cells and a range of prostate carcinoma cell lines derived from human tumors. We have observed elevated expressions of HSF1, HSP60, and HSP70 in the aggressively malignant cell lines PC-3, DU-145, and CA-HPV-10. Elevated HSP expression in cancer cell lines appeared to be regulated at the post-messenger ribonucleic acid (mRNA) levels, as indicated by gene chip microarray studies, which indicated little difference in heat shock factor (HSF) or HSP mRNA expression between the normal and malignant prostate cell lines. When we compared the expression patterns of constitutive HSP genes between PC-3 prostate carcinoma cells growing as monolayers in vitro and as tumor xenografts growing in nude mice in vivo, we found a marked reduction in expression of a wide spectrum of the HSPs in PC-3 tumors. This decreased HSP expression pattern in tumors may underlie the increased sensitivity to heat shock of PC-3 tumors. However, the induction by heat shock of HSP genes was not markedly altered by growth in the tumor microenvironment, and HSP40, HSP70, and HSP110 were expressed abundantly after stress in each growth condition. Our experiments indicate therefore that HSF and HSP levels are elevated in the more highly malignant prostate carcinoma cells and also show the dominant nature of the heat shock-induced gene expression, leading to abundant HSP induction in vitro or in vivo.

Animals↗
PubMed2005

[Anti-tumor effect of pcDNA3. 1-Egr. 1p-p16 gene combined with radiotherapy in tumor-bearing nude mice].

OBJECTIVE: To investigate the optimal doses of X-ray irradiation and plasmid injection in the anti-tumor effect of the pcDNA3. 1-Egr. 1p-p16 gene combined with radiotherapy in vivo. METHODS: We observed the anti-tumor effect of the pcDNA3. 1-Egr. 1p-p16 gene combined with radiotherapy with different doses of X-ray irradiation (2, 10, 20 Gy) and plasmid injection (10, 20, 30 microg) in nude mice with JF-305 pancreatic carcinoma, and detected the expression of p16 in tumor by RT-PCR. RESULTS: The tumor growth rate of the nude mice irradiated locally with 20 Gy X-rays after the plasmid injection was significantly lower (P < 0.05 ) than that of the nude mice irradiated locally with 2 Gy or 10 Gy X-ray 3 days after the irradiation. The tumor growth rate of the nude mice injected locally with 20 microg or 30 microg plasmid was significantly lower (P <0.05 ) than that of the nude mice injected locally with 10 microg plasmid. Both pcDNA3. 1-Egr. 1p-p16 group and pcDNA3. 1-Egr. 1p-p16 +20 Gy group had p16 mRNA expression, but the mRNA level of pcDNA3. 1-Egr. 1p-p16 +20 Gy group was higher than that of pcD- NA3. 1-Egr. 1p-p16 group. CONCLUSION: In the pcDNA3. 1-Egr. 1p-p16 gene combined with radiotherapy in vivo the optimal dose of X-ray irradiation was 20 Gy and the optimal dose of plasmid injection was 20 microg. The anti-tumor effect of pcDNA3. 1-Egr. 1p-p16 combined with radiotherapy is better than that of radiotherapy or gene therapy alone, which may be related with the enhanced p16 expression in tumor after the irradiation.

Animals↗
PubMed2005

[Cytomegalovirus infection accompanied with acute pancreatitis after kidney transplantation].

OBJECTIVE: To explore the prevention and management of human cytomegalovirus (HCMV) infection accompanied with acute pancreatitis after kidney transplantation. METHODS AND RESULTS: A retrospective analysis of 5 patients with acute pancreatitis after kidney transplantation was conducted. The incidence of acute pancreatitis after kidney transplantation was 2.3% (5/217). All the 5 cases were complicated by active HCMV infection, 3 of which had hyperlipemia and 2 had liver dysfunction. Three cases were finally cured while the other 2 died, one of which was due to respiration failure arising from HCMV interstitial pneumonia accompanied with hemorrhagic necrotizing pancreatitis, and the other due to fulminating liver function failure because of active HCMV infection accompanied with hemorrhagic necrotizing pancreatitis. CONCLUSION: Active HCMV infection is the most important factor responsible for acute pancreatitis, and early diagnosis and treatment are crucial to lower mortality rate.

Adult↗