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Biomedical subjects

Min Wu

Publications and source records attributed to Min Wu.

At least 55 records · Page 3Linked to original sources
PubMed2005

Overexpression of stefin A in human esophageal squamous cell carcinoma cells inhibits tumor cell growth, angiogenesis, invasion, and metastasis.

PURPOSE: Evidence is accumulating that an inverse correlation exists between stefin A level and malignant progression. The aim of this study is to investigate the role of stefin A in human esophageal squamous cell carcinoma cells and to evaluate the possibility of stefin A for cancer therapy. EXPERIMENTAL DESIGN: We stably transfected stefin A cDNA into human EC9706 or KYSE150 esophageal squamous cell carcinoma cells. Subsequently, we evaluated the effect of stefin A overexpression on cell growth, cathepsin B activity, cell motility and invasion, tumor growth, and metastasis. Immunoanalysis was done to assess the expression of factor VIII and to support the localization of stefin A and cathepsin B. We also evaluated the effect of CA074Me, a selective membrane-permeant cathepsin B inhibitor. RESULTS: Both transfection of stefin A and treatment with 10 micromol/L CA074Me significantly reduced cathepsin B activity and inhibited the Matrigel invasion. Combination of both further reduced cathepsin B activity and inhibited the Matrigel invasion. Overexpression of stefin A delayed the in vitro and in vivo growth of cells and significantly inhibited lung metastasis compared with 50% of lung metastasis in xenograft mice from EC9706 or empty vector cells. Transfection with stefin A showed a dramatic reduction of factor VIII staining in the tumors of xenograft mice. CONCLUSIONS: Our data strongly indicate that stefin A plays an important role in the growth, angiogenesis, invasion, and metastasis of human esophageal squamous cell carcinoma cells and suggest that stefin A may be useful in cancer therapy.

Animals↗
PubMed2005

Significance of COX-2 expression in human esophageal squamous cell carcinoma.

Cyclooxygenase-2 (COX-2) is well established to play an important role in the tumorigenesis of a variety of human cancers; however, the function of COX-2 in the development of esophageal squamous cell carcinoma (ESCC) remains less clear. Here, we determined, first, the pattern of COX-2 expression in normal esophageal mucosa, dysplasia, carcinoma in situ (CIS) and invasive SCC. Immunohistochemical analysis showed that, while COX-2 was weakly expressed, if at all, in normal squamous epithelium, strong COX-2 expression was detected as early as the stage of dysplasia and frequently in 20 of 26 (77%) CIS and 86 of 111 (77%) invasive SCC. Upregulation of COX-2 in ESCC was found to be significantly associated with tumor progression (R = 0.493, P < 0.01). Further, treatment of human ESCC cell lines (KYSE450 and KYSE510) with NS-398, a COX-2 specific chemical inhibitor, suppressed the production of prostaglandin E2 (PGE2) and induced cell growth inhibition, cell cycle arrest at the G1-S checkpoint, and the expression of cyclin-dependent kinase inhibitors p21waf1/cip1 and p27kip1. Finally, knockdown expression of COX-2 in KYSE450 cells by a specific COX-2 siRNA dramatically inhibited PGE2 production, cell growth and, more importantly, colony formation and tumorigenesis in nude mice. Together, this study suggested that COX-2 may be involved in an early stage of squamous cell carcinogenesis of the esophagus and has a non-redundant role in the regulation of cellular proliferation and tumorigenesis of esophageal epithelial cells.

Animals↗
PubMed2005

Alteration of RPL14 in squamous cell carcinomas and preneoplastic lesions of the esophagus.

Allelic loss on chromosome 3p occurs frequently in esophageal cancer. The human ribosomal protein L14 gene (RPL14) is located on chromosome 3p21.3. In the present study, we investigated alteration of RPL14 at both the genomic DNA and RNA levels in 129 Chinese esophageal squamous cell carcinomas (ESCC) and 17 dysplasia adjacent to tumor tissues by a combination of tissue microdissection, microsatellite analysis of the intragenic marker, reverse transcriptase-polymerase chain reaction (RT-PCR) and direct sequencing. In the tested informative cases, loss of heterozygosity (LOH) of RPL14 was observed in 29 out of 68 (43%) tumors. Decreased expression of the gene was detected in 31 out of 49 (63%) carcinomas. No mutation was found in the remaining RPL14 allele of the tumors with LOH. We examined subsequently the allelic status of RPL14 in the dysplasia (preneoplastic lesions) between malignant tissues and histologically normal epithelia. Of 17 tested dysplasia in which the tumors showed LOH, eight (47%) displayed the same allelic loss as their corresponding tumors, seven (41%) exhibited microsatellite instability (MSI), and only two retained both the RPL14 alleles. The data suggest that alteration of RPL14 occurred frequently in ESCC and might be an earlier event in the tumorigenesis of the esophagus. Analysis to RPL14 gene may contribute to the early detection of ESCC as a potential molecular marker.

Adult↗
PubMed2005

Omega-3 polyunsaturated fatty acids attenuate breast cancer growth through activation of a neutral sphingomyelinase-mediated pathway.

The effect of fish oils and their active omega-3 fatty acid constituents, docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), were investigated on breast cancer growth. In in vivo experiments, mice were fed diets that were rich in either omega-3 (fish oil) or omega-6 (corn oil) fatty acids. Three weeks after implantation of MDA-MB-231 breast cancer cells, the tumor volume and weight were significantly lower (p < 0.05) for mice fed the omega-3 diets compared to those fed the omega-6 diets. Dietary fish oil also caused a 40% (p < 0.05) increase in neutral sphingomyelinase (N-SMYase) activity in the tumors. The tumor tissues from fish oil-fed animals expressed elevated p21 (waf1/cip1) mRNA, whereas tumor tissues from corn oil-fed animals exhibited undetectable levels of p21 expression. In in vitro experiments, at concentrations as low as 25 muM, DHA and EPA inhibited the growth of cultured MDA-MB-231 cells in a dose-dependent manner by 20-25% (p < 0.05). N-SMYase activity was also increased by 30-40% (p < 0.05) in the DHA- or EPA-treated cells in which an increase in ceramide formation was observed. DHA and EPA were both observed to enhance membrane bleb formation and also to induce the expression of p21. Omega-3 fatty acids-induced bleb formation and p21 expression were inhibited by the N-SMYase inhibitor GW4869, which also inhibited apoptosis by approximately 40% (p < 0.05). The results suggest that inhibition of breast cancer growth in nude mice by dietary fish oil and inhibition of breast cancer cell growth in culture by treatment with DHA and EPA is mediated by activation of N-SMYase.

Animal Feed↗
PubMed2005

Tumorigenic properties of neurofibromin-deficient Schwann cells in culture and as syngrafts in Nf1 knockout mice.

Neurofibromatosis type 1 (NF1) is one of the most common dominantly inherited genetic diseases associated with the nervous system. Functional loss of the NF1 tumor suppressor is frequently associated with the generation of benign neurofibromas that can progress to malignancy. Recent evidence in genetic mouse models indicates that the development of neurofibromas requires a loss of Nf1 in the cells destined to become neoplastic as well as heterozygosity in nonneoplastic cells. We tested this hypothesis in a newly developed syngraft mouse model in which Nf1-/- Schwann cells isolated from knockout embryos were grafted into the sciatic nerves of Nf1+/- mice, corresponding to the genetic background of NF1 patients. Furthermore, we also characterized in vitro growth of these cells. We found that embryonic mouse Nf1-/- Schwann cells exhibit increased proliferation and less growth factor-dependence in vitro compared with heterozygous and wild-type counterparts. Moreover, Nf1-/- Schwann cells showed tumorigenic growth when implanted into nerve of adult Nf1 heterozygous mice. These findings support the conclusion that loss of Nf1 in embryonic mouse Schwann cells is sufficient for tumor development in the heterozygous environment of adult mouse nerve. In addition, this syngraft model provides a practical means for the controlled induction of neurofibromas, greatly facilitating localized application of therapeutic agents and gene delivery.

Animals↗
PubMed2005

Synthesis and structure-activity relationship of N-alkyl Gly-boro-Pro inhibitors of DPP4, FAP, and DPP7.

The structure-activity relationship of various N-alkyl Gly-boro-Pro derivatives against three dipeptidyl peptidases (DPPs) was studied. In a series of N-cycloalkyl analogs, DPP4 and fibroblast activation protein-alpha (FAP) optimally preferred N-cycloheptyl whereas DPP7 tolerated even larger cycloalkyl rings. Gly alpha-carbon derivatization of N-cyclohexyl or N-(2-adamantyl) Gly-boro-Pro resulted in a significant decrease in potency against all the three DPPs.

Adenosine Deaminase Inhibitors↗
PubMed2005

Boro-norleucine as a P1 residue for the design of selective and potent DPP7 inhibitors.

Dipeptide-based inhibitors with C-substituted (alkyl or aminoalkyl) alpha-amino acids in the P2 position and boro-norleucine (boro-Nle) in the P1 position were synthesized. Relative to boro-proline, boro-Nle as a P1 residue was shown able to significantly dial out DPP4, FAP, DPP8, and DPP9 activity. Dab-boro-Nle (4g) proved to be the most selective and potent DPP7 inhibitor with a DPP7 IC50 value of 480 pM.

Boronic Acids↗
PubMed2005

Detection of chromosomal alterations in bladder transitional cell carcinomas from Northern China by comparative genomic hybridization.

To identify chromosome alterations in Chinese bladder cancer, forty-six transitional cell carcinomas of the bladder were analyzed by comparative genomic hybridization. Frequent gains of DNA copy number were observed on 1p (13/46), 1q (13/46), 5p (8/46), 6p (9/46), 7p (7/46), 8q (12/46), 11q (8/46), 17q (11/46), 19q (7/46), 20q (8/46) and Yq (8/46), with minimal overlapping regions at 1p32-pter (10/46), 1q21-q24 (12/46), 5p (8/46), 6p22-p23 (7/46), 7p11.2-p14 (7/46), 8q22-q24 (12/46), 11q13-q14 (8/46), 17q22-qter (11/46), 19q11-13.2 (7/46), 20q11-q13.2 (8/46) and Yq11 (8/46). Losses were predominantly found on 2q (16/46), 5q (8/46), 8p (7/46), 9p (8/46), 9q (13/46), 11p (7/46), 13q (7/46), 17p (12/46), 18q (7/46), Xp (18/46) and Xq (19/46), with smallest overlapping regions at 2q32-qter (16/46), 5q12-q31 (8/46), 8p12-pter (7/46), 9p21-pter (10/46), 9q (13/46), 11p (7/46), 13q13-q22 (7/46), 17p (12/46), 18q21-qter (7/46), Xp (18/46) and Xq (19/46). There were significantly higher frequencies of gains of 1q21-q24 and 17q22-qter in moderately differentiated tumors as compared with those in well-differentiated tumors, indicating a possible association of these two abnormalities with the dedifferentiation of tumor cells. Gains of 1p32-pter, 5p, 6p22-p23, 11q13-q14, 17q22-qter and losses of 2q32-qter, 9q, 17p were more frequent in pT1 as compared with those in pTa carcinomas. Gains at 1q21-q24, 7p11.2-p14, 8q22-q24, 19q, 20q11-q13.2 and losses at 5q12-q31, 8p12-pter, 9p21-pter, 11p, 13q13-q22 and 18q21-qter were unique to pT1 and higher stage tumors, suggesting that genes responsible for the invasion and progression of bladder cancer might be located at these chromosomal regions. In multiple tumors from the same patients, consistent alterations such as gains of 8q, 11q13-q14, 12q13-q15, 13q12, 20q and losses of 2q32-qter, 8p, 9, 11p, 11q21-qter, 13q13-qter, X were detected. These abnormalities were possibly earlier events, which might play a critical role during the genesis of the tumors. Further detailed studies to the recurrent aberration regions may lead to the identification of oncogenes and tumor suppressor genes involved in the development and progression of Chinese bladder cancer.

Adult↗
PubMed2005

Lipid segregation and IgE receptor signaling: a decade of progress.

Recent work to characterize the roles of lipid segregation in IgE receptor signaling has revealed a mechanism by which segregation of liquid ordered regions from disordered regions of the plasma membrane results in protection of the Src family kinase Lyn from inactivating dephosphorylation by a transmembrane tyrosine phosphatase. Antigen-mediated crosslinking of IgE receptors drives their association with the liquid ordered regions, commonly called lipid rafts, and this facilitates receptor phosphorylation by active Lyn in the raft environment. Previous work showed that the membrane skeleton coupled to F-actin regulates stimulated receptor phosphorylation and downstream signaling processes, and more recent work implicates cytoskeletal interactions with ordered lipid rafts in this regulation. These and other results provide an emerging view of the complex role of membrane structure in orchestrating signal transduction mediated by immune and other cell surface receptors.

Animals↗
PubMed2005

Anticancer properties of propofol-docosahexaenoate and propofol-eicosapentaenoate on breast cancer cells.

INTRODUCTION: Epidemiological evidence strongly links fish oil, which is rich in docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), with low incidences of several types of cancer. The inhibitory effects of omega-3 polyunsaturated fatty acids on cancer development and progression are supported by studies with cultured cells and animal models. Propofol (2,6-diisopropylphenol) is the most extensively used general anesthetic-sedative agent employed today and is nontoxic to humans at high levels (50 microg/ml). Clinically relevant concentrations of propofol (3 to 8 microg/ml; 20 to 50 microM) have also been reported to have anticancer activities. The present study describes the synthesis, purification, characterization and evaluation of two novel anticancer conjugates, propofol-docosahexaenoate (propofol-DHA) and propofol-eicosapentaenoate (propofol-EPA). METHODS: The conjugates linking an omega-3 fatty acid, either DHA or EPA, with propofol were synthesized and tested for their effects on migration, adhesion and apoptosis on MDA-MB-231 breast cancer cells. RESULTS: At low concentrations (25 microM), DHA, EPA or propofol alone or in combination had minimal effect on cell adhesion to vitronectin, cell migration against serum and the induction of apoptosis (only 5 to 15% of the cells became apoptotic). In contrast, the propofol-DHA or propofol-EPA conjugates significantly inhibited cell adhesion (15 to 30%) and migration (about 50%) and induced apoptosis (about 40%) in breast cancer cells. CONCLUSION: These results suggest that the novel propofol-DHA and propofol-EPA conjugates reported here may be useful for the treatment of breast cancer.

Antineoplastic Agents↗
PubMed2005

High spatial resolution observation of single-molecule dynamics in living cell membranes.

Self-organized lipid bilayers together with proteins are the essential building blocks of biological membranes. Membranes are associated with all living systems as they make up cell boundaries and provide basic barriers to cellular organelles. It is of interest to study the dynamics of individual molecules in cell membranes as the mechanism of how biological membranes function at the single molecule remains to be elucidated. In this letter we describe a study in which we incubate rat basophilic leukemia cells with a fluorescently labeled cell membrane component on a surface containing zero-mode waveguides (ZMWs). We used the ZMW to confine fluorescent excitation to an approximately 100-nm region of the membrane to monitor lipid diffusion along the cellular membrane. We showed that confinement with a ZMW largely reduced fluorescent contributions from the cytosolic pool that is present when using a more standard technique such as laser-induced confocal microscopy. We show that optical confinement with ZMWs is a facile way to probe dynamic processes on the membrane surface.

Animals↗
PubMed2005

[Expression of MLRQ subunit gene of NADH oxidoreductase and its clinical significance in malignant tumors of digestive system].

OBJECTIVE: To study the differential expression and possible role of MLRQ subunit gene of nicotinamide adenine dinucleotide reduced (NADH) oxidoreductase in malignant tumors of digestive system. METHODS: Specimens of cancerous tissues and matched adjacent normal tissues resected during operation or biopsy: 38 pairs of specimens of esophageal carcinoma, 7 pairs of specimens of cardiac carcinoma, 14 pairs of specimens of gastric carcinoma, 11 pairs of specimens of colon carcinoma, and 7 pairs of specimens of liver carcinoma underwent PCR test and Northern hybridization to detect the differential expression of MLRQ subunit gene of NADH oxidoreductase. RESULTS: (1) Overexpression of MLRQ subunit gene was found in 31 of the 38 pairs of specimens of esophageal carcinoma (81.6%), 4 of the 7 pairs of specimens of cardiac carcinoma (57.1%), 12 of the 14 pairs of specimens of gastric carcinoma (85.7%), 4 of the 7 pairs of specimens of colon carcinoma (65.6%), and 7 of the 11 pairs of specimens of liver cancer (57.1%). No significant difference among different cancers was observed by X(2) test (all P > 0.05). (2) The up-regulation of MLRQ subunit was not correlated with clinic stage, infiltration degree, lymphatic metastasis, and differentiation of tumor (all P > 0.05). CONCLUSION: MLRQ subunit gene is up-regulated in the malignant tumors of digestive system.

Digestive System Neoplasms↗
PubMed2005

The expression of intact and mutant human apoAI/CIII/AIV/AV gene cluster in transgenic mice.

The apoAI/CIII/AIV gene cluster is involved in lipid metabolism and has a complex pattern of gene expression modulated by a common regulatory element, the apoCIII enhancer. A new member of this cluster, apolipoprotein (apo) AV, has recently been discovered as a novel modifier in triglyceride metabolism. To determine the expression of all four apo genes in combination and, most importantly, whether the transcription of apoAV is coregulated by the apoCIII enhancer in the cluster, we generated an intact transgenic line carrying the 116-kb human apoAI/CIII/AIV/AV gene cluster and a mutant transgenic line in which the apoCIII enhancer was deleted from the 116-kb structure. We demonstrated that the apoCIII enhancer regulated hepatic and intestinal apoAI, apoCIII, and apoAIV expression; however, it did not direct the newly identified apoAV in the cluster. Furthermore, human apo genes displayed integrated position-independent expression and a closer approximation of copy number-dependent expression in the intact transgenic mice. Because apoCIII and apoAV play opposite roles in triglyceride homeostasis, we analyzed the lipid profiles in our transgenic mice to assess the effects of human apoAI gene cluster expression on lipid metabolism. The triglyceride level was elevated in intact transgenic mice but decreased in mutant ones compared with nontransgenic mice. In addition, the expression of human apoAI and apoAIV elevated high density lipoprotein cholesterol in transgenic mice fed an atherogenic diet. In conclusion, our studies with human apoAI/CIII/AIV/AV gene cluster transgenic models showed that the apoCIII enhancer regulated expression of apoAI, apo-CIII, and apoAIV but not apoAV in vivo and showed the influences of expression of the entire cluster on lipid metabolism.

Animals↗
PubMed2005

B23 regulates GADD45a nuclear translocation and contributes to GADD45a-induced cell cycle G2-M arrest.

Gadd45a is an important player in cell cycle G2-M arrest in response to genotoxic stress. However, the underlying mechanism(s) by which Gadd45a exerts its role in the control of cell cycle progression remains to be further defined. Gadd45a interacts with Cdc2, dissociates the Cdc2-cyclin B1 complex, alters cyclin B1 nuclear localization, and thus inhibits the activity of Cdc2/cyclin B1 kinase. These observations indicate that Gadd45a nuclear translocation is closely associated with its role in cell cycle G2-M arrest. Gadd45a has been characterized as a nuclear protein, but it does not contain a classical nuclear localization signal, suggesting that Gadd45a nuclear translocation might be mediated through different nuclear import machinery. Here we show that Gadd45a associates directly with B23 (nucleophosmin), and the B23-interacting domain is mapped at the central region (61-100 amino acids) of the Gadd45a protein using a series of Myc tag-Gadd45a deletion mutants. Deletion of this central region disrupts Gadd45a association with B23 and abolishes Gadd45a nuclear translocation. Suppression of endogenous B23 through a short interfering RNA approach disrupts Gadd45a nuclear translocation and results in impaired Gadd45a-induced cell cycle G2-M arrest. These findings demonstrate a novel association of B23 and Gadd45a and implicate B23 as an important regulator in Gadd45a nuclear import.

Active Transport, Cell Nucleus↗
PubMed2005

[The effect and mechanism of arsenic trioxide on hepatocellular carcinoma].

OBJECTIVE: To investigate the effect and mechanism of arsenic trioxide on hepatoma cell line BEL-7402 and observe the effect and best administration method of arsenic trioxide on hepatocellular carcinoma patients who were not suitable for operation. METHODS: The cell activity and morphologic changes were studied after being treated with arsenic trioxide in different concentrations. The apoptosis was detected by flow cytometry assay and DNA fragmentation assay. The caspase-3 level of mRNA and protein were detected by reverse transcription polymerase chain reaction (RT-PCR) and fluoro-spectrophotometer. The growth inhibition of implant tumor was observed in nude mice treated with arsenic trioxide in different concentrations. Arsenic trioxide was used in hepatocellular carcinoma patients by intravenous dropping and continuous regional infusion through hepatic artery. RESULTS: The effect of arsenic trioxide on hepatoma cell lines was dependent on the time and concentration obviously. The decrease in cell number was preceded by morphological changes in the treated BEL-7402 cells that were characteristic of apoptosis, including membrane blebbing, shrunken cytoplasm, nuclear condensation and loss of adhesion. Flow cytometry assay showed an arrestment at G(2)/M phase and sub-G(1) cell peak. DNA fragmentation assay showed a marked DNA ladder. The mRNA level of caspase-3 was no change in RT-PCR whereas the protein of caspase-3 was increased after added As(2)O(3) 1 - 36 h. Caspase-3 activity began to increase after 2 h and reached a maximal level after 12 h in a linear fashion. Then, the level of caspase-3 was decreased, but still in a high level. The growth inhibition of implant tumors was obviously in nude mice. The intravenous usage of arsenic trioxide could improve the quality of life with low toxicity in hepatocellular carcinoma patients not suitable for operation. The tumor size decreased in 30 patients and AFP value decreased in 19 patients by continuous regional infusion through hepatic artery. CONCLUSIONS: Arsenic trioxide can obviously inhibit the growth of hepatoma cell line BEL-7402 through inducing hepatoma cell apoptosis. The activation and increase of Caspase-3 is the possible mechanism of apoptosis, and the acting point is in pro-enzyme level. The best result of arsenic trioxide on non-operative patients should be gotten in continuous infusion through hepatic artery.

Adult↗
PubMed2005

Up-regulation of fibronectin in oesophageal squamous cell carcinoma is associated with activation of the Erk pathway.

Fibronectin (FN) was found to be up-regulated in human oesophageal squamous cell carcinoma (ESCC) by cDNA microarray analysis in our laboratory. In order to elucidate the chronology of FN expression at various stages of oesophageal carcinogenesis, RT-PCR, immunohistochemistry and Western blot analysis were carried out on ESCC tissue samples with different pathological characteristics. FN was mainly localized in the interstitial tissues, and its up-regulation in ESCC was significantly associated with the depth of invasion by carcinoma (R = 0.803, p < 0.01). To investigate its relationship with the Erk pathway further, pRaf-1 and pErk-1/2 expression were also analysed in ESCC. Activation of Erk1/2 and Raf was identified in 63.3% and 60.3% of the tumour specimens, respectively, whereas normal mucosal epithelial tissues were negative. Moreover, a close association was observed between pErk-1/2 expression and the differentiation grade (R = -0.421, p = 0.002): pErk-1/2 signal was greater in poorly differentiated tissues than in well and moderately differentiated tissues. Co-expression of FN and pErk-1/2 was found at the invasive front of tumour nests by double immunofluorescence staining and there was a statistical correlation between the expression of FN and pErk-1/2 (p < 0.05). In the cell line EC9706, plasma FN was able to phosphorylate Raf and further activate Erk, but it did not alter MMP-2 protein expression or activity, indicating that MMP-2 may not be the downstream target gene of the Erk pathway. All the above data suggest that the up-regulation of FN contributes to the later stage of oesophageal carcinogenesis, and that activation of the Erk pathway may be involved in the roles of FN in ESCC.

Blotting, Western↗
PubMed2005

Public health data collection and sharing using HIPAA messages.

Public health information has significant value for doctors, public health officials, epidemiological researchers, the general public, and government agencies. Unfortunately, these data are difficult to obtain and are typically collected on as-needed basis and maintained locally. This localized process unavoidably limits the access to important public health data by its users. Moreover, the diversity of data transmission standards and collection techniques make the collected data less usable. This paper proposes a new standardized public health information system based on the HIPAA (Health Insurance Portability and Accountability Act) messages, which are the standard transactions between hospitals and insurance companies. In particular, this paper explores the applicability of HIPAA messages as a data source and transmission standard, and proposes a prototype design of a new system to collect and share public health data using HIPAA messages.

Data Collection↗