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Yanping Wang

Publications and source records attributed to Yanping Wang.

46 records · Page 3Linked to original sources

The interleukin-1 family of cytokines and receptors in human breast cancer: implications for tumor progression.

We have previously described the expression of interleukin cytokines (IL)-1alpha, IL-1beta, and IL-1 receptor antagonist (IL-1ra) in human breast cancer (HBC) tissue. Based on our previous studies, we hypothesize that the IL-1 family of cytokines, antagonists (IL-1ra) and receptors (IL-1RI and IL-1RII) are present within the human breast cancer (HBC) tumor microenvironment and that the IL-1 network of cytokines and receptors within the tumor microenvironment can control tumor cell subpopulation expression of other protumorigenic cytokines such as the angiogenic/growth factor, interleukin-8 (IL-8). To test this hypothesis we characterized the in vivo expression of the IL-1 network in HBC tissues and homogenates by immunohistochemistry (IHC) and ELISA. Additionally, we examined IL-1R expression in HBC cell lines in vitro and in a murine xenograft model by IHC. Finally, we determined the ability of IL-1 to induce IL-8 expression in in vitro using HBC cell lines. We observed that not only are the IL-1 cytokines present in HBC tissue and homogenates, but that IL-1Rs and IL-8 are also present in the HBC tumor microenvironment. Additionally, expression levels for some members of the IL-1/IL-8 network of cytokines correlated with the prognostic indicators, ER/PR. Using HBC cell lines, we observed that HBC cell lines express IL-1Rs in vitro and in the xenograft model. Furthermore, in vitro, HBC cell lines show a spectrum of responsiveness to IL-1 as measured by expression the proangiogenic/mitogenic cytokine IL-8. Our data clearly demonstrate the presence and distribution of IL-1 cytokines and receptors in HBC and suggests that the local expression of IL-1 results in the activation of a population of cells within the HBC tumor microenvironment. This activation of the IL-1/IL-1R cytokine family via autocrine and/or paracrine mechanisms leads to a cascade of secondary protumorigenic cytokines. These secondary signals induce the expression of numerous protumorigenic activities such as the expression of IL-8, and subsequently contribute to angiogenesis, tumor proliferation, and tumor invasion.

Animals↗

FR901228, an inhibitor of histone deacetylases, increases the cellular responsiveness to IL-6 type cytokines by enhancing the expression of receptor proteins.

The related members of the interleukin-6 (IL-6) family of cytokines, leukemia inhibitory factor (LIF), oncostatin M (OSM) and IL-6 are inflammatory mediators that control differentiated cell functions as well as proliferation. The cellular responsiveness to these cytokines is largely determined by the expression of the appropriate receptor proteins. The receptor expression profile for each cell type is established during differentiation and is often altered during oncogenic transformation. Since inhibition of histone deacetylases (HDAC) has the potential to re-activate epigenetically silenced genes, we asked whether inhibition of HDAC enhances the expression of IL-6 cytokine receptors and, thus, increase desirable cytokine responses. We demonstrate that treatment with FR901228 (FR), an HDAC inhibitor, increases the responsiveness to LIF in different cell types, including normal fibroblasts, epithelial cells, macrophages and splenocytes, as well as various tumor cell lines. Depending on the cell type, FR treatment also enhances the responsiveness to OSM and IL-6. These effects involve a transcriptional induction of the cytokine receptor subunits LIFRalpha, OSMRbeta, gp130, or the transcription factor STAT3. FR-specific induction of LIFRalpha occurs independently of de novo protein synthesis and cell proliferation and is mediated in part by the CBP/p300 coactivator. Chromatin immunoprecipitation experiments indicate that the expression of LIFRalpha and gp130 genes correlates with the level of acetylated histone 3 associated with the receptor promoter regions. The FR-stimulated expression of IL-6-type cytokine receptors in certain tumor cells also provided improved conditions for suppression of cell growth by taking advantage of the growth inhibitory effect of these cytokines.

Acetylation↗

Functional diversification during evolution of the murine alpha(1)-proteinase inhibitor family: role of the hypervariable reactive center loop.

Alpha(1)-proteinase inhibitor (alpha(1)-PI) is a member of the serpin superfamily of serine proteinase inhibitors that are involved in the regulation of a number of proteolytic processes. Alpha(1)-PI, like most serpins, functions by covalent binding to, and inhibition of, target proteinases. The interaction between alpha(1)-PI and its target is directed by the so-called reactive center loop (RCL), an approximately 20 residue domain that extends out from the body of the alpha(1)-PI polypeptide and determines the inhibitor's specificity. Mice express at least seven closely related alpha(1)-PI isoforms, encoded by a family of genes clustered at the Spi1 locus on chromosome 12. The amino acid sequence of the RCL region is hypervariable among alpha(1)-PIs, a phenomenon that has been attributed to high rates of evolution driven by positive Darwinian selection. This suggests that the various isoforms are functionally diverse. To test this notion, we have compared the proteinase specificities of individual alpha(1)-PIs from each of the two mouse species. As predicted from the positive Darwinian selection hypothesis, the various alpha(1)-PIs differ in their ability to form covalent complexes with serine proteinases, such as elastase, trypsin, chymotrypsin, and cathepsin G. In addition, they differ in their binding ability to proteinases in crude snake venoms. Importantly, the RCL region of the alpha(1)-PI polypeptide is the primary determinant of isoform-specific differences in proteinase recognition, indicating that hypervariability within this region drives the functional diversification of alpha(1)-PIs during evolution. The possible physiological benefits of alpha(1)-PI diversity are discussed.

Amino Acid Sequence↗

Consequences of divorce on the adjustment of children in China.

Explored the consequences of divorce on children in China. In contrast to Western countries, divorce in China is relatively rare, occurring in approximately 10% to 15% of the population. Children from divorced families (n = 174) and matched intact families (n = 174) were selected from a larger sample of 1,294 children between 8 and 14 years of age. Divorce was relatively low in this sample (13.45%) of participants, consistent with rates observed in epidemiological studies in China. Mothers of divorced children reported higher levels of education but lower levels of income than mothers in intact families. Children in divorced families reported higher levels of anxiety and depression, and their mothers and teachers rated them as possessing more behavior problems on the Achenbach (1991) Child Behavior Checklist scales. Regression analyses revealed that rejecting and inattentive parenting styles, along with family status (divorce or intact), high maternal depression, and sex (boys) predicted significant amounts of variance associated with these negative outcomes. Results are discussed in terms of familial and cultural issues associated with these findings.

Adolescent↗

[Effects of ectogenous FHIT gene on reversing malignant phenotype of human lung adenocarcinoma cells A549].

OBJECTIVE: To explore the role of fragile histidine triad(FHIT) gene in the proliferation, apoptosis and tumorigenesis of human lung cancer cells. METHODS: FHIT gene packaged with lipofectin was transfected into the cells of a human lung adenocarcinoma cell line (A549), which stably expressed ectogenous FHIT gene. The FHIT mRNA and protein expression of A549-FHIT, A549-vector and A549 cell were detected by reverse transcription-PCR(RT-PCR), Western blot and immunocytochemical methods. The cell cycle pattern and apoptosis were assayed by using flow cytometry. RESULTS: After transfection of FHIT gene, cell growth was obviously inhibited (P<0.01). The apoptosis index of A549-FHIT (8.42%) was significantly higher than that of A549-vector (5.45%) and A549 cells (5.71%)(P<0.01). The clone-formation rate of A549-FHIT cell (21.84%) was significantly lower than that of A549-vector (28.70%) and A549 cells (31.68%, P<0.01). Compared with control cell lines, larger scale of A549-FHIT cells accumulated in G0/G1, presenting that the proportion of the cells in G0/G1 phase was obviously increased from 67.78 % to 82.35 %. Tumorigenicity of the A549 cells in nude mice was greatly inhibited by expression of ectogenous FHIT gene, the weight and volume of A549-FHIT(1.61 g/1.37 cm(3)) were significantly lower than that of A549-vector (2.45 g/1.99cm(3)) and A549 cells (2.77 g/2.27 cm(3))(P<0.05). CONCLUSION: Expression of ectogenous FHIT gene can obviously inhibit the proliferation and tumorigenesis of A549 cells, and can induce A549 cells into programmed cell death. The result of this study suggests that FHIT gene may be a tumor suppressor gene in human lung cancer cells.

Acid Anhydride Hydrolases↗

[Mutational analysis of MECP2 gene in Rett syndrome].

OBJECTIVE: To investigate mutations of MECP2 gene in classical sporadic Rett syndrome (RTT) patients in China. METHODS: Polymerase chain reaction, single strand conformation polymorphism, cloning and direct sequencing were employed to analyse the three exons of MECP2 gene in 26 RTT patients and their parents, and in 2 sisters of 2 of the RTT patients. RESULTS: Nine different mutations in exon 3 were identified in 14 of the 26 patients with RTT, including 3 missense mutations, 3 nonsense mutations, and 3 frame-shift mutations (2 deletion mutations and 1 insert mutation); 2 of these were novel. A missense variant was also identified, which was carried by unaffected father and affected daughter. CONCLUSION: Mutations in MECP2 gene were found over 50% of patients with RTT in China.

Base Sequence↗

[A study on apoptosis of nasopharyngeal carcinoma cell line induced by Tanshinone II A and its molecular mechanism].

OBJECTIVE: To assess effect of Tanshinone II A on the apoptosis of human nasopharyngeal carcinoma (NPC) cell line CNE-1 and inquire into the mechanism there in involved. METHODS: The CNE-1 cells cultured in vitro were treated with 0.5 microgram/ml Tanshinone II A for 4 days. The morphology of the cells was observed by microscopy. The cell growth and proliferation were measured by cell counting. The DNA break was examined by gel electrophoresis. The cell cycle, apoptosis index (AI) and the expression of apoptosis associated gene were analysed by flow cytometry. RESULTS: 0.5 microgram/ml Tanshinone II A could induce the apoptosis of CNE-1 cells. In the treatment group, the morphologic characteristics of apoptotic cells were observed, the DNA of cells presented "ladder" break, the cell growth and proliferation were inhibited obviously, and the AI was 16.9% (the AI of control group was 6.4%). The cells were arrested in G0/G1 phase and cellular DNA synthesis was inhibited. The expressions of apoptosis associated gene fas, bax, p53 and p21 were up-regulated; the expression of bcl-2 was down-regulated. CONCLUSION: Tanshinone II A can induce apoptosis of human nasopharyngeal carcinoma cells. Its molecular mechanism may relate to modulation of the apoptosis associated gene expression.

Abietanes↗

[An epidemiological investigation of perinatal teratomas in China].

OBJECTIVE: To investigate the prevalence rate and epidemiological features of teratomas in China. METHODS: From 1987 through 1992, hospital-based cluster sampling method was adopted for collecting data. During that period all live or still births with 28 weeks of gestation or more were assessed within 7 days after delivery. RESULTS: 238 teratoma cases were identified in 4,489,692 births, including 198 isolated and 40 associated forms of teratomas. The prevalence rates of total teratomas, isolated and associated forms of teratomas were 0. 53/10000, 0.44/10000, 0.09/10000 respectively. The prevalence rates in urban areas and rural areas were 0.46/10000 and 0.66/10000, respectively. The prevalence rates of teratomas in male and female births were 0.80/10000 and 0.27/10000 correspondingly. The ratio of male to female teratomas was 1:2.76. The perinatal fatality rate of teratomas was 55.0%. CONCLUSION: The most frequent teratomas were isolated forms. Time trends have not been found in the occurrence of teratomas. High prevalence in urban areas has been observed, compared to that in rural areas. The prevalence of teratomas in female births is three times as high as that in male births. In view of the high fatality rate, prenatal diagnosis and perinatal management of teratomas should be strengthened.

China↗

[Dynamic monitoring of neural tube defects in China during 1996 to 2000].

OBJECTIVE: The database from Chinese Birth Defects Monitoring Network was used to describe the epidemiological features and secular trends of neural tube defects (NTDs) prevalence during Jan. 1996 to Dec. 2000, including anencephaly, spina bifida and encephalocele. METHODS: Data were collected with hospital-based cluster sampling method. During the period, all live or still births with 28 weeks or more of gestation were assessed within seven days after delivery. RESULTS: There were 2 873 case with NTDs identified from 2 281 616 births, with an overall prevalence rate of 12.95 per 10,000 births. And, the prevalence rates of anencephaly, spina bifida and encephalocele were 5.02 per 10,000, 6.30 per 10,000 and 1.64 per 10,000, respectively. Significant falls in overall prevalence rates of NTDs and of anencephaly were observed. The prevalence rates of NTDs were 9.75 per 10,000 and 15.96 per 10,000 in male and female births, respectively, 7.76 per 10,000 and 25.20 per 10,000 in the urban and rural areas, respectively, and 19.90 per 10,000 and 5.81 per 10,000 in north and south China, respectively. The prevalence was higher in the groups with maternal age of less than 20 years and more than 30 years than in those other maternal ages. Preterm babies and babies with low birth weight accounted for 50.9% and 50.6% of perinatal babies with NTDs, respectively, with a perinatal mortality of 77.8%. CONCLUSIONS: In China, the occurrence of NTDs was higher in female births than in male births, higher in the rural than in the urban, and higher in the north than in the south. Annual prevalence rate of NTDs in China presented a declining trend, but still higher than that in the other countries at the same time period. Babies with NTDs were in poor birth quality, higher perinatal mortality and poor prognosis. Effective preventive measures and prenatal diagnosis should be strengthened to reduce the occurrences of neural tube defects.

Adult↗

Ischemia-reperfusion injury causes oxidative stress and apoptosis of Schwann cell in acute and chronic experimental diabetic neuropathy.

Mild ischemia-reperfusion (IR) injury to diabetic peripheral nerve is known to cause severe ischemic fiber degeneration. Little information is available on its effects on Schwann cell (SC). In this study, we evaluated oxidative stress and apoptosis of SC following mild IR, using immunohistochemistry in streptozotocin (STZ)- induced diabetic rats. Twenty-six rats were divided into four groups according to the duration of diabetes: 1- month STZ-induced diabetic group (n=7) and age-matched control group (n=7); 4-month STZ-induced diabetic group (n=6) and age-matched control group (n=6). Using our established IR model of 3 h of ischemia followed by 7 days of reperfusion, sciatic and tibial nerves were harvested and labeled with 8-hydroxydeoxyguanosine (8-OHdG; oxidative stress marker), caspase-3 (apoptotic executor), and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) activity (apoptotic indicator). Marked positive staining with 8-OHdG, caspase-3, and TUNEL were found in diabetic ischemic nerves (right side) following IR in both 1-month and 4-month groups. Only mild positive staining or no staining was seen in the nonischemic side (left side) of diabetic and age-matched control groups. Co-labeling with S-100 confirmed that the cells labeled with 8-OHdG, caspase3, and TUNEL were SC. SC was susceptible to oxidative injury and apoptosis in experimental diabetic neuropathy when subjected to mild IR injury.

8-Hydroxy-2'-Deoxyguanosine↗