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Ping Liang

Publications and source records attributed to Ping Liang.

At least 37 records · Page 2Linked to original sources

A comparison of the aging and apoptotic transcriptome of Saccharomyces cerevisiae.

In this paper, we present the results of global transcript analysis by the microarray technique of senescent and apoptotic yeast cells. We compared young daughter and old mother cells isolated by elutriation centrifugation, and non-apoptotic and apoptotic cells induced either by a temperature shift of the cdc48(S565G) temperature-sensitive mutant or of the orc2-1 temperature-sensitive mutant. The majority of all genes found to be differentially regulated in these three physiological situations was upregulated, indicating that a cellular death process was initiated rather than an unspecific shut-down of gene expression due to immediate killing. The functional classes of genes upregulated in all three conditions were largely the same, although individual genes were in many cases not identical. The largest group of genes involved were nuclear genes coding for mitochondrial components or functions, which is understandable given the fact that apoptosis can be triggered by mitochondrially generated oxygen radicals and that mitochondria play an important role in the execution of apoptosis. Other functional classes consisted of genes involved in DNA damage response, in cell cycle regulation and checkpoints, in DNA repair, and in membrane lipid and cell wall synthesis. These functional classes represent the response of the cell to the known cellular insults, which occur during aging and apoptosis. As we have shown previously, final-stage senescent yeast mother cells (of the wild-type) are apoptotic.

Apoptosis↗

Genomic rearrangements by LINE-1 insertion-mediated deletion in the human and chimpanzee lineages.

Long INterspersed Elements (LINE-1s or L1s) are abundant non-LTR retrotransposons in mammalian genomes that are capable of insertional mutagenesis. They have been associated with target site deletions upon insertion in cell culture studies of retrotransposition. Here, we report 50 deletion events in the human and chimpanzee genomes directly linked to the insertion of L1 elements, resulting in the loss of approximately 18 kb of sequence from the human genome and approximately 15 kb from the chimpanzee genome. Our data suggest that during the primate radiation, L1 insertions may have deleted up to 7.5 Mb of target genomic sequences. While the results of our in vivo analysis differ from those of previous cell culture assays of L1 insertion-mediated deletions in terms of the size and rate of sequence deletion, evolutionary factors can reconcile the differences. We report a pattern of genomic deletion sizes similar to those created during the retrotransposition of Alu elements. Our study provides support for the existence of different mechanisms for small and large L1-mediated deletions, and we present a model for the correlation of L1 element size and the corresponding deletion size. In addition, we show that internal rearrangements can modify L1 structure during retrotransposition events associated with large deletions.

Animals↗

Construction and clinical significance of a predictive system for prognosis of hepatocellular carcinoma.

AIM: The aims of this study were to explore individualized treatment method for hepatocellular carcinoma (HCC) patients whose maximum tumor size was less than 5 cm to improve prognosis and survival quality. METHODS: Thirty cases of primary HCC patients undergoing tumor resection were retrospectively analyzed (resection group). All the tumors were proved as primary HCC with pathologic examination. The patients were divided into two groups according to follow-up results: group A, with tumor recurrence within 1 year after resection; group B, without tumor recurrence within 1 year. Immunohistochemical stainings were performed using 11 kinds of monoclonal antibodies (AFP, c-erbB2, c-met, c-myc, HBsAg, HCV, Ki-67, MMP-2, nm23-H1, P53, and VEGF), and expressing intensities were quantitatively analyzed. Regression equation using factors affecting prognosis of HCC was constructed with binary logistic method. HCC patients undergoing percutaneous microwave coagulation therapy (PMCT) were also retrospectively analyzed (PMCT group). Immunohistochemical stainings of tumor biopsy samples were performed with molecules related to HCC prognosis, staining intensities were quantitatively analyzed, coincidence rate of prediction was calculated. RESULTS: In resection group, the expressing intensities of c-myc, Ki-67, MMP-2 and VEGF in cancer tissue in group A were significantly higher than those in group B (t = 2.97, P = 0.01; t = 2.42, P = 0.03<0.05; t = 2.57, P = 0.02<0.05; t = 3.43, P = 0.004<0.01, respectively); the expressing intensities of 11 kinds of detected molecules in para-cancer tissue in groups A and B were not significantly different (P>0.05). The regression equation predicting prognosis of HCC is as follows: P(1) = 1/[1+e(-(3.663-0.412mycc-2.187Ki-67c-0.397vegfc))]. It demonstrates that prognosis of HCC in resection group was related with c-myc, Ki-67 and VEGF expressing intensity in cancer tissue. In PMCT group, the expressing intensities of c-myc, Ki-67 and VEGF in cancer tissue in group A were significantly higher than those in group B (t = 4.57, P = 0.000<0.01; t = 2.08, P = 0.04<0.05; t = 2.38, P = 0.02<0.05, respectively); the expressing intensities of c-myc, Ki-67 and VEGF in para-cancer tissue in groups A and B were not significantly different (P>0.05). The coincidence rate of patients undergoing PMCT in group A was 88.00% (22/25), in group B 68.75% (11/16), the total coincidence rate was 80.49% (33/41). CONCLUSION: The regression equation is accurate and feasible and could be used for predicting prognosis of HCC, it helps to select treatment method (resection or PMCT) for HCC patients to realize individualized treatment to improve prognosis.

Adult↗

Alu retrotransposition-mediated deletion.

Alu repeats contribute to genomic instability in primates via insertional and recombinational mutagenesis. Here, we report an analysis of Alu element-induced genomic instability through a novel mechanism termed retrotransposition-mediated deletion, and assess its impact on the integrity of primate genomes. For human and chimpanzee genomes, we find evidence of 33 retrotransposition-mediated deletion events that have eliminated approximately 9000 nucleotides of genomic DNA. Our data suggest that, during the course of primate evolution, Alu retrotransposition may have contributed to over 3000 deletion events, eliminating approximately 900 kb of DNA in the process. Potential mechanisms for the creation of Alu retrotransposition-mediated deletions include L1 endonuclease-dependent retrotransposition, L1 endonuclease-independent retrotransposition, internal priming on DNA breaks, and promiscuous target primed reverse transcription. A comprehensive analysis of the collateral effects by Alu mobilization on all primate genomes will require sequenced genomes from representatives of the entire order.

Alu Elements↗

Prognostic factors for survival in patients with hepatocellular carcinoma after percutaneous microwave ablation.

PURPOSE: To determine the long-term survival and prognostic factors in patients with hepatocellular carcinoma treated with percutaneous microwave ablation. MATERIALS AND METHODS: Institutional review board approval and informed consent were obtained. A database of cases of hepatocellular carcinoma in 288 patients (259 men, 29 women; mean age, 54.8 years +/- 11.4 [standard deviation]; age range, 25-82 years) with 477 histologically proved lesions who underwent percutaneous microwave coagulation therapy between May 1994 and October 2002 was retrospectively analyzed. Prognostic factors for survival were evaluated by means of univariate and multivariate analyses. RESULTS: The mean follow-up period after microwave ablation was 31.41 months +/- 20.43 (range, 5-106 months). The 1-, 2-, 3-, 4-, and 5-year cumulative survival rates among all 288 patients were 93%, 82%, 72%, 63%, and 51%, respectively. Ninety-three patients (32%) died. Local recurrence or new tumors occurred in 100 patients (35%). Age (P = .836), sex (P = .073), preablation serum alpha-fetoprotein level (P = .136), and preablation treatment (P = .256) were not related to prognosis, while tumor number (P = .004), tumor size (P < .001), Child-Pugh classification (P = .003), tumor differentiation (P = .026), and local recurrence or presence of new tumors (P = .004) significantly affected survival at univariate analysis. At multivariate analysis, only tumor size (P < .001), number of nodules (P = .005), and Child-Pugh classification (P = .01) each had a significant effect on survival. CONCLUSION: With use of microwave ablation, there is a high probability of long-term survival of patients with a single lesion of 4.0 cm or less in maximum diameter and Child-Pugh class A cirrhosis.

Adult↗

Phosphatidylcholine-rich acceptors, but not native HDL or its apolipoproteins, mobilize cholesterol from cholesterol-rich insoluble components of human atherosclerotic plaques.

To examine the potential of high density lipoproteins (HDL) to ameliorate atherosclerotic plaques in vivo, we examined the ability of native HDL, lipid-free HDL apolipoproteins (apo HDL), cholesterol-free discoidal reconstituted HDL (R-HDL) comprised of apo HDL and phosphatidylcholine (PC) and PC liposomes to release cholesterol from cholesterol-rich insoluble components of plaques (ICP) isolated from atherosclerotic human aorta. Isolated ICP had a free cholesterol (FC) to phospholipid (PL) mass ratio (0.8-3.1) and a sphingomyelin (SPM) to PC mass ratio (1.2-4.2) that exceeded those of plasma membranes of cultured cells. Surprisingly, native HDL and its apolipoproteins were not able to release cholesterol from ICP. However, R-HDL and PC liposomes were effectively released cholesterol from ICP. The release of ICP cholesterol by R-HDL was dose-dependent and accompanied by the transfer of > 8 x more PC in the reverse direction (i.e., from R-HDL to ICP), resulting in a marked enrichment of ICP with PC. Compared to R-HDL, PC liposomes were significantly less effective in releasing cholesterol from ICP but were somewhat more effective in enriching ICP with PC. Native HDL was minimally effective in enriching ICP with PC, but became effective after prior in vitro enrichment of HDL with PC from multilamellar PC liposomes. The enrichment of ICP with PC resulted in the dissolution of cholesterol crystals on ICP and allowed the removal of ICP cholesterol by apo HDL and plasma. Our study revealed that the removal of cholesterol from ICP in vivo will be possible through a change in the level, composition, and physical state of ICP lipids mediated by PC-enriched HDL.

Aorta↗

Molecular mechanism of inhibition of survivin transcription by the GC-rich sequence-selective DNA binding antitumor agent, hedamycin: evidence of survivin down-regulation associated with drug sensitivity.

Expression of the antiapoptotic protein survivin is associated with cancer cell viability and drug resistance. Thus, control of its expression in cancer cells has significant consequences for cancer therapeutics. Here we have shown that hedamycin, a GC-rich DNA binding drug, down-regulated survivin expression. Using a series of survivin promoter-luciferase constructs, we have identified an 86-bp GC-rich DNA element (-124 to -39) that mediates the ability of hedamycin to down-regulate survivin expression. Furthermore, both in vivo foot-printing and in vitro gel mobility shift experiments revealed that hedamycin bound to a 21-bp GC-rich DNA element (-115 to -95) in the survivin promoter. This drug-DNA interaction abrogated the binding of Sp-1 or Sp1-like proteins to the 21-bp cis-acting DNA element, and mutagenesis of this region consistently diminished survivin promoter activity. Finally, down-regulation of survivin transcription by hedamycin modulated the viability of cancer cells. These data suggest that abrogation of Sp-1 or Sp1-like protein binding to the 21-bp DNA element in the survivin promoter contributes at least in part to the inhibitory effect of hedamycin on survivin gene transcription. Drug-induced modulation of survivin gene expression may provide novel approaches for cancer therapeutics.

Anthraquinones↗

The 5' region of the MSH2 gene involved in hereditary non-polyposis colorectal cancer contains a high density of recombinogenic sequences.

MSH2 rearrangements are involved in approximately 10% of hereditary non-polyposis colorectal cancer (HNPCC) families, and in most of the rearrangements, exon 1 is deleted. We scanned by quantitative multiplex polymerase chain reaction (PCR) of short fluorescent fragments (QMPSF) 200 kb of genomic sequences upstream of the MSH2 transcription initiation site in 21 HNPCC families with exon 1 deletions. This QMPSF scan revealed 12 distinct 5' breakpoints located up to 200 kb upstream of the MSH2 transcription initiation site. Sequencing analysis of the rearranged allele in 17 families revealed that most of the deletions (15/17) resulted from homologous Alu-mediated recombination. QMPSF and sequencing analysis in these 21 families led us to detect the presence of 20 distinct 5' breakpoints. In 14 out of 15 Alu-mediated recombinations, we found, either within the identical region in which the recombination had probably occurred or in its vicinity, the 26-bp Alu core sequence containing the recombinogenic Chi-like motif. Compared to the equivalent regions of other human genes, the MSH2 upstream region was found to contain a high density of Alu repeats (30% within 228 kb and 43% within 50 kb), most of which belong to the old Alu S subfamilies. In conclusion, this study demonstrates the heterogeneity of the breakpoints within the MSH2 upstream region and reveals the remarkable density of recombinogenic Alu sequences in this region.

Adult↗

Sonography-guided percutaneous microwave ablation of high-grade dysplastic nodules in cirrhotic liver.

OBJECTIVE: Our objective was to evaluate the effect of sonography-guided percutaneous microwave ablation of high-grade dysplastic nodules in the cirrhotic liver. MATERIALS AND METHODS: From July 1997 to May 2003, 49 histologically proven high-grade dysplastic nodules in 30 patients with liver cirrhosis were treated by microwave ablation. Three patients had concomitant small hepatocellular carcinomas (D < 3.0 cm), whereas another three had undergone liver segmentectomy for hepatocellular carcinoma 1 year earlier. The mean size of the nodules was 1.8 cm (range, 0.9-4.6 cm). Sixty-eight insertions with 78 applications were administered to the 49 nodules. RESULTS: The follow-up period was 12-82 months (mean, 45.1 +/- 19.0 months). Five patients died during this study: three from advanced hepatocellular carcinoma, one from bleeding in the upper gastrointestinal tract, and another from cerebral hemorrhage. All nodules showed decreased density on unenhanced CT and no enhancement on contrast-enhanced CT after microwave ablation. Posttreatment biopsy performed in 16 patients with 18 nodules 1-3 months after microwave ablation showed no evidence of viable tissue but replacement by fibrotic tissue in all nodules. CONCLUSION: Percutaneous microwave ablation as a minimally invasive therapy is effective for ablating high-grade dysplastic nodules, thus preventing their potential malignant transformation, which may improve survival. The preliminary data warrant further prospective, randomized studies.

Adult↗

[Expression and significance of angiopoietins in oral squamous cell carcinoma].

OBJECTIVE: To observe the expression of angiopoietins in oral squamous cell carcinoma and relationship between the expression of angiopoietins and pathologic classification. METHODS: The expression of Ang-1 and Ang-2 protein in samples from 42 oral squamous cell carcinoma and 16 oral normal mucosa were detected by immunohistochemical technique. RESULTS: The expression of Ang-1 and Ang-2 was found in both oral squamous cell carcinoma and normal control. It was found Ang-1 expression alike in oral squamous cell carcinoma and control (P > 0.05). Ang-2 expressed at low level in control while strongly positive in oral squamous cell caroinoma and the level of Ang-2 expression in oral squamous cell caroinoma was related to pathologic classification (P < 0.05). CONCLUSION: Ang-2 expression in oral squamous cell carcinoma is related to angiogenesis and pathological classification, which is probably involved in angiogenesis regulation, promotes the development and metastasis of oral squamous cell carcinoma.

Angiopoietin-1↗

[Study on expression of PS1 in APP-PS1 double gene stably transfected cell lines and its relation to gamma-secretase].

OBJECTIVE: To study the role of presenilin1 (PS1) in the processing of beta-amyloid precursor protein (APP) to amyloid beta-peptide (Abeta) and its relation to gamma-secretase in the pathogenesis of Alzheimer's disease (AD). METHODS: Several CHO cell lines stably transfected with either wide-type or mutant PS1 (M(146)L) along with APP(751) genes were established. The expression of PS1 and its half-life were determined by immunoprecipitation, Western blotting and pulse-chase experiment. Abeta released into the conditional media was quantitated by ELISA. RESULTS: PS1 transfected CHO cells expressed an expected 45,000 full length protein. This over-expressed full length PS1 was subject to fast degradation with a half-life of less than 1 hour. In contrast to full length PS1, the truncated N-terminal and C-terminal proteins of PS1 were significantly more stable with a longer half-life of nearly 16 hours. Although the total amount of Abeta released into the conditional media did not show a significant difference between wild-type and mutant PS1 (M(146)L) transfected APP cells, mutant PS1 (M(146)L) transfected APP cells increase Abeta(1 - 42) (a subspecies of total Abeta) production with nearly a 2 fold increase, comparing to untransfected or wild-type PS1 transfected APP cells. CONCLUSION: PS1 is involved in the processing of APP to Abeta, a nearly 2 fold increase of Abeta production in mutant PS1 (M(146)L) transfected APP cells indicates that PS1 may be the expected gamma-secretase itself.

Alzheimer Disease↗

Structure-function evolution of the transforming acidic coiled coil genes revealed by analysis of phylogenetically diverse organisms.

BACKGROUND: Examination of ancient gene families can provide an insight into how the evolution of gene structure can relate to function. Functional homologs of the evolutionarily conserved transforming acidic coiled coil (TACC) gene family are present in organisms from yeast to man. However, correlations between functional interactions and the evolution of these proteins have yet to be determined. RESULTS: We have performed an extensive database analysis to determine the genomic and cDNA sequences of the TACCs from phylogenetically diverse organisms. This analysis has determined the phylogenetic relationship of the TACC proteins to other coiled coil proteins, the resolution of the placement of the rabbit TACC4 as the orthologue of human TACC3, and RHAMM as a distinct family of coiled coil proteins. We have also extended the analysis of the TACCs to the interaction databases of C. elegans and D. melanogaster to identify potentially novel TACC interactions. The validity of this modeling was confirmed independently by the demonstration of direct binding of human TACC2 to the nuclear hormone receptor RXRbeta. CONCLUSION: The data so far suggest that the ancestral TACC protein played a role in centrosomal/mitotic spindle dynamics. TACC proteins were then recruited to complexes involved in protein translation, RNA processing and transcription by interactions with specific bridging proteins. However, during evolution, the TACC proteins have now acquired the ability to directly interact with components of these complexes (such as the LSm proteins, nuclear hormone receptors, GAS41, and transcription factors). This suggests that the function of the TACC proteins may have evolved from performing assembly or coordination functions in the centrosome to include a more intimate role in the functional evolution of chromatin remodeling, transcriptional and posttranscriptional complexes in the cell.

Alternative Splicing↗

Effect of c-myc, Ki-67, MMP-2 and VEGF expression on prognosis of hepatocellular carcinoma patients undergoing tumor resection.

AIM: To explore the effect of c-myc, Ki-67, MMP-2 and VEGF expression on prognosis of hepatocellular carcinoma (HCC) patients undergoing tumor resection. METHODS: Primary HCC patients underwent tumor resection were retrospectively analysed. The maximum size of the tumor was less than 5 cm, there was only one nodule in each patient. No chemoembolization was performed before resection. They were followed up after resection, and the time of recurrence was recorded. They were divided into 2 groups: group A (15 cases): tumor recurrence within 1 year after tumor resection, and group B (15 cases): with or without tumor recurrence 2 years after tumor resection. Pathological slices were made with tumor wax-sample. Immunohistochemistry staining was performed with c-myc, Ki-67, MMP-2 and VEGF monoclonal antibodies. Staining intensity was quantitatively analysed with a pathological diagram-writing analyzing system. The expressing intensity differences of stained molecules in cancer tissue and para-cancer were analysed. RESULTS: c-myc, Ki-67, MMP-2 and VEGF expressing intensities in cancer tissue in group A were higher than those in group B (P values were 0.010, 0.030, 0.022 and 0.004, respectively), but they were not significantly different in para-cancer tissue in groups A and B (P values were 0.334, 0.343, 0.334 and 0.334, respectively). CONCLUSION: The expression of c-myc, Ki-67, MMP-2 and VEGF in cancer tissue is related to the recurrence of HCC after tumor resection.

Adult↗

Postprandial chylomicrons: potent vehicles for transporting cholesterol from endogenous LDL+HDL and cell membranes to the liver via LCAT and CETP.

We examined whether postprandial (PP) chylomicrons (CMs) can serve as vehicles for transporting cholesterol from endogenous cholesterol-rich lipoprotein (LDL+HDL) fractions and cell membranes to the liver via lecithin:cholesterol acyltransferase (LCAT) and cholesteryl ester transfer protein (CETP) activities. During incubation of fresh fasting and PP plasma containing [(3)H]cholesteryl ester (CE)-labeled LDL+HDL, both CMs and VLDL served as acceptors of [(3)H]CE or cholesterol from LDL+HDL. The presence of CMs in PP plasma suppressed the ability of VLDL to accept [(3)H]CE from LDL+HDL. In reconstituted plasma containing an equivalent amount of triglycerides from isolated VLDL or CMs, a CM particle was about 40 times more potent than a VLDL particle in accepting [(3)H]CE or cholesterol from LDL+HDLs. When incubated with red blood cells (RBCs) as a source for cell membrane cholesterol, the cholesterol content of CMs, VLDL, LDL, and HDL in PP plasma increased by 485%, 74%, 13%, and 30%, respectively, via LCAT and CETP activities. The presence of CMs in plasma suppressed the ability of endogenous lipoproteins to accept cholesterol from RBCs. Our data suggest that PP CMs may play an important role in promoting reverse cholesterol transport in vivo by serving as the preferred ultimate vehicle for transporting cholesterol released from cell membranes to the liver via LCAT and CETP.

Adult↗

Genomic characterization and expression analysis of the first nonmammalian renin genes from zebrafish and pufferfish.

Renin is a key enzyme in the renin-angiotensin system (RAS), a pathway which plays an important physiological role in blood pressure and electrolyte homeostasis. The origin of the RAS is believed to have accompanied early evolution of vertebrates. However, renin genes have so far only been unequivocally identified in mammals. Whether or not a bona fide renin gene exists in nonmammalian vertebrates has been an intriguing question of physiological and evolutionary interest. Using a genomic analytical approach, we identified renin genes in two nonmammalian vertebrates, zebrafish (Danio rerio) and pufferfish (Takifugu rubripes). Phylogenetic analysis demonstrates that the predicted fish renins cluster together with mammalian renins to form a distinct subclass of vertebrate aspartyl proteases. RT-PCR results confirm generation of the predicted zebrafish mRNA and its expression in association with the opisthonephric kidney of adult zebrafish. Comparative in situ hybridization analysis of wild-type and developmental mutants indicates that renin expression is first detected bilaterally in cells of the interrenal primordia at 24 h postfertilization, which subsequently migrate to lie adjacent to, but distinct from, the glomerulus of the developing pronephric kidney. Our report provides the first molecular evidence for the existence of renin genes in lower vertebrates. The observation that the earliest renin-expressing cells, arising during ontogeny of this teleost vertebrate, are of adrenocortical lineage raises an interesting hypothesis as regards the origin of renin-expressing cells in the metanephric kidney of higher vertebrates.

Adrenal Glands↗

Organ distribution of severe acute respiratory syndrome (SARS) associated coronavirus (SARS-CoV) in SARS patients: implications for pathogenesis and virus transmission pathways.

We previously identified the major pathological changes in the respiratory and immune systems of patients who died of severe acute respiratory syndrome (SARS) but gained little information on the organ distribution of SARS-associated coronavirus (SARS-CoV). In the present study, we used a murine monoclonal antibody specific for SARS-CoV nucleoprotein, and probes specific for a SARS-CoV RNA polymerase gene fragment, for immunohistochemistry and in situ hybridization, respectively, to detect SARS-CoV systematically in tissues from patients who died of SARS. SARS-CoV was found in lung, trachea/bronchus, stomach, small intestine, distal convoluted renal tubule, sweat gland, parathyroid, pituitary, pancreas, adrenal gland, liver and cerebrum, but was not detected in oesophagus, spleen, lymph node, bone marrow, heart, aorta, cerebellum, thyroid, testis, ovary, uterus or muscle. These results suggest that, in addition to the respiratory system, the gastrointestinal tract and other organs with detectable SARS-CoV may also be targets of SARS-CoV infection. The pathological changes in these organs may be caused directly by the cytopathic effect mediated by local replication of the SARS-CoV; or indirectly as a result of systemic responses to respiratory failure or the harmful immune response induced by viral infection. In addition to viral spread through a respiratory route, SARS-CoV in the intestinal tract, kidney and sweat glands may be excreted via faeces, urine and sweat, thereby leading to virus transmission. This study provides important information for understanding the pathogenesis of SARS-CoV infection and sheds light on possible virus transmission pathways. This data will be useful for designing new strategies for prevention and treatment of SARS.

Adult↗