Search PubMed⌕ Search

Biomedical subjects

Yong Liu

Publications and source records attributed to Yong Liu.

At least 181 records · Page 10Linked to original sources
PubMed2003

Functional identification of distinct sets of antitumor activities mediated by the FKBP gene family.

Assigning biologic function to the many sequenced but still uncharacterized genes remains the greatest obstacle confronting the human genome project. Differential gene expression profiling routinely detects uncharacterized genes aberrantly expressed in conditions such as cancer but cannot determine which genes are functionally involved in such complex phenotypes. Integrating gene expression profiling with specific modulation of gene expression in relevant disease models can identify complex biologic functions controlled by currently uncharacterized genes. Here, we used systemic gene transfer in tumor-bearing mice to identify novel antiinvasive and antimetastatic functions for Fkbp8, and subsequently for Fkbp1a. Fkbp8 is a previously uncharacterized member of the FK-506-binding protein (FKBP) gene family down-regulated in aggressive tumors. Antitumor effects produced by Fkbp1a gene expression are mediated by cellular pathways entirely distinct from those responsible for antitumor effects produced by Fkbp1a binding to its bacterially derived ligand, rapamycin. We then used gene expression profiling to identify syndecan 1 (Sdc1) and matrix metalloproteinase 9 (MMP9) as genes directly regulated by Fkbp1a and Fkbp8. FKBP gene expression coordinately induces the expression of the antiinvasive Sdc1 gene and suppresses the proinvasive MMP9 gene. Conversely, short interfering RNA-mediated suppression of Fkbp1a increases tumor cell invasion and MMP9 levels, while down-regulating Sdc1. Thus, syndecan 1 and MMP9 appear to mediate the antiinvasive and antimetastatic effects produced by FKBP gene expression. These studies show that uncharacterized genes differentially expressed in metastatic cancers can play important functional roles in the metastatic phenotype. Furthermore, identifying gene regulatory networks that function to control tumor progression may permit more accurate modeling of the complex molecular mechanisms of this disease.

Animals↗
PubMed2003

Possible mechanisms underlying the protective effects of SY-21, an extract of a traditional Chinese herb, on transient brain ischemia/reperfusion-induced neuronal death in rat hippocampus.

We examined the neuroprotective actions of SY-21, a potent ingredient of a traditional Chinese herb, histologically. Transient brain ischemia (15 min) was induced by four-vessel occlusion in Sprague-Dawley rats. Administration of SY-21 20 min before or 6 h after brain ischemia significantly increased the number of surviving hippocampal CA1 pyramidal cells in rats subjected to transient brain ischemia followed by 5 days of reperfusion. Neuronal cell death resulting from ischemic events is associated with abnormal activation of the NMDA receptors. Tyrosine phosphorylation of the NMDA receptor subunit NR2A by Src or Fyn has been implicated in the up-regulation of NMDA receptor activity. In order to investigate the possible mechanism of the neuroprotective action of SY-21, we examined the effects of SY-21 on the ischemia/reperfusion-induced increases in tyrosine phosphorylation of the NMDA receptor subunit 2A (NR2A) and on the interactions involving NR2A, PSD-95 and Src/Fyn. We found that the increase in the tyrosine phosphorylation of NR2A induced by brain ischemia/reperfusion is suppressed by SY-21 administered 15 min before, or instantly after, brain ischemia. Also, SY-21 attenuated the increased interactions involving NR2A, PSD-95, Fyn and Src. These results demonstrate that SY-21 has a prominent neuroprotective action against brain ischemic insult, and the mechanism may involve the regulation of the tyrosine phosphorylation of NR2A by changing the above interactions.

Animals↗
PubMed2003

Id-1 as a molecular target in therapy for breast cancer cell invasion and metastasis.

Mammary epithelial cells constitutively expressing Id-1 protein are unable to differentiate, acquire the ability to proliferate, and invade the extracellular matrix. In addition, Id-1 is aberrantly over-expressed in aggressive and metastatic breast cancer cells, as well as in human breast tumor biopsies from infiltrating carcinomas, suggesting Id-1 might be an important regulator of breast cancer progression. We show that human metastatic breast cancer cells become significantly less invasive in vitro and less metastatic in vivo when Id-1 is down-regulated by stable transduction with antisense Id-1. Expression of the matrix metalloproteinase MT1-MMP is decreased in proportion to the decrease in Id-1 protein levels, representing a potential mechanism for the reduction of invasiveness. Further, to more accurately recapitulate the biology of and potential therapeutic approaches to tumor metastasis, we targeted Id-1 expression systemically in tumor-bearing mice by using a nonviral approach. We demonstrate significant reduction of both Id-1 and MT1-MMP expressions as well as the metastatic spread of 4T1 breast cancer cells in syngeneic BALB/c mice. In conclusion, our studies have identified Id-1 as a critical regulator of breast cancer progression and suggest the feasibility of developing novel therapeutic approaches to target Id-1 expression to reduce breast cancer metastasis in humans.

Animals↗
PubMed2003

Two types of calcium channels regulating activation of proline-rich tyrosine kinase 2 induced by transient brain ischemia in rat hippocampus.

Tyrosine phosphorylation is an important means for regulating post-ischemic signal transduction. In this article, brain ischemia was induced by four-vessel occlusion, and the effect of ischemia/reperfusion on proline-rich tyrosine kinase 2 (Pyk2) was studied. Tyrosine phosphorylation of Pyk2 in Sprague-Dawley rat hippocampus after transient (15 min) brain ischemia and reperfusion was examined by immunoprecipitation and immunoblot. Kinase activity of Pyk2 was examined by the method of (32)P-incorporation into poly(Glu-Tyr). Tyrosine phosphorylation and kinase activity of Pyk2 decreased slightly after ischemia, then increased after reperfusion and reached the peak levels (5.1 and 1.8 times the levels of the sham-operated group, respectively) at 1 h of reperfusion. Both the increases were partly inhibited by NMDA receptor antagonist ketamine and L-type voltage-gated calcium channel antagonist nifedipine administered 20 min before ischemia. The results suggested that Pyk2 was activated after transient brain ischemia and reperfusion, and it might play an important role in mediating post-ischemic signal transduction events.

Animals↗
PubMed2003

The adeno-associated virus major regulatory protein Rep78-c-Jun-DNA motif complex modulates AP-1 activity.

Multiple epidemiologic studies show that adeno-associated virus (AAV) is negatively associated with cervical cancer (CX CA), a cancer which is positively associated with human papillomavirus (HPV) infection. Mechanisms for this correlation may be by Rep78's (AAV's major regulatory protein) ability to bind the HPV-16 p97 promoter DNA and inhibit transcription, to bind and interfere with the functions of the E7 oncoprotein of HPV-16, and to bind a variety of HPV-important cellular transcription factors such as Sp1 and TBP. c-Jun is another important cellular factor intimately linked to the HPV life cycle, as well as keratinocyte differentiation and skin development. Skin is the natural host tissue for both HPV and AAV. In this article it is demonstrated that Rep78 directly interacts with c-Jun, both in vitro and in vivo, as analyzed by Western blot, yeast two-hybrid cDNA, and electrophoretic mobility shift-supershift assay (EMSA supershift). Addition of anti-Rep78 antibodies inhibited the EMSA supershift. Investigating the biological implications of this interaction, Rep78 inhibited the c-Jun-dependent c-jun promoter in transient and stable chloramphenicol acetyl-transferase (CAT) assays. Rep78 also inhibited c-Jun-augmented c-jun promoter as well as the HPV-16 p97 promoter activity (also c-Jun regulated) in in vitro transcription assays in T47D nuclear extracts. Finally, the Rep78-c-Jun interaction mapped to the amino-half of Rep78. The ability of Rep78 to interact with c-Jun and down-regulate AP-1-dependent transcription suggests one more mechanism by which AAV may modulate the HPV life cycle and the carcinogenesis process.

Blotting, Western↗
PubMed2003

Hypermethylation of p16INK4a in Chinese lung cancer patients: biological and clinical implications.

Promoter hypermethylation of the p16INK4a gene was investigated in 111 cases of tumor tissue, as well as in 136 circulating plasma and 95 sputum samples from Chinese patients with primary lung cancer, using a modified protocol of semi-nested methylation-specific-PCR (MSP). The results showed hypermethylated p16 sequence in 80.2% of tumor tissues and frequencies of 75.7 and 74.7% in plasma and sputum specimens, respectively. Among the patients, 50 cases of matched plasma, sputum and tumor tissue from the same individual were analyzed. Of these, hypermethylation of the p16 promoter was detected in 84.0% of the tumor tissues, with frequencies of 72.0 and 76.0% in the corresponding plasma and sputum, respectively. Notably, only patients whose tumor tissue showed hypermethylation of p16 exhibited the same aberrant methylation in their sputum and/or plasma. Hypermethylation of p16 in sputum and plasma samples may provide a more sensitive approach to molecular diagnosis of lung cancer than relying on conventional cytological analysis. Our data show that a combination of cytological analysis of sputum and examination of p16 hypermethylation in sputum and plasma identified 92.0% (46/50) of the lung cancer patients studied, offering an effective means of early detection of lung cancer.

Adenocarcinoma↗
PubMed2003

Increased tyrosine phosphorylation of alpha(1C) subunits of L-type voltage-gated calcium channels and interactions among Src/Fyn, PSD-95 and alpha(1C) in rat hippocampus after transient brain ischemia.

It has been reported that the Src family kinases-mediated tyrosine phosphorylation of alpha(1C) subunits of L-type voltage-gated calcium channels (L-VGCCs) potentiates the channel currents. In this study, we evaluated the alterations in the tyrosine phosphorylation level of alpha(1C) and in the interactions involving Src/Fyn, alpha(1C) and PSD-95 in the hippocampus after transient (15 min) brain ischemia followed by various times of reperfusion using immunoprecipitation and immunoblotting. Transient brain ischemia was induced by the method of four-vessel occlusion in Sprague-Dawley rats. The tyrosine phosphorylation level of alpha(1C) subunits elevated immediately after brain ischemia. The elevation in phosphorylation sustained for at least 6 h and peaked at 15 min of reperfusion. Transient brain ischemia and reperfusion also caused rapid and sustained increases in the interactions of Src and Fyn with alpha(1C) subunits. More interestingly, co-immunoprecipitation analysis showed that 15 min of reperfusion dramatically increased the interaction between PSD-95 and alpha(1C) and promoted the formation of alpha(1C)-PSD-95-Src complexes, for the first time. The protein levels of alpha(1C), Src, Fyn and PSD-95 showed no differences at all time points. These results suggest a novel mechanism involving the ischemia/reperfusion-induced recruitment of L-VGCCs, Src and Fyn to the PSD-95 signaling complex that facilitates the tyrosine phosphorylation of alpha(1C) subunits by Src family kinases and may contribute to the up-regulation of L-VGCCs activity in postischemic hippocampus.

Animals↗
PubMed2003

Testing recombinant adeno-associated virus-gene loading of dendritic cells for generating potent cytotoxic T lymphocytes against a prototype self-antigen, multiple myeloma HM1.24.

Recent studies demonstrate that recombinant adeno-associated virus (rAAV)-based antigen loading of dendritic cells (DCs) generates significant and rapid (one stimulation per week) cytotoxic T-lymphocyte (CTL) responses in vitro against viral antigens. As a more extensive analysis of the rAAV system, we have used a self-antigen, HM1.24, expressed in multiple myeloma (MM). Again, with one stimulation, significant major histocompatibility complex (MHC) class 1-restricted, anti-HM1.24-specific CTL killing was demonstrated against MM cells. Furthermore, higher expression of interferon-gamma (IFN-gamma) in T cells and higher expression levels of, in order of significance, CD80 (2.6- to 3.8-fold increase), CD86, and CD40 on DCs were also observed. The use of synthetic HM1.24-positive target cells further demonstrated the antigen specificity of these CTLs. There was also no evidence of natural killer cell involvement. These data extend our earlier studies and suggest that the rAAV-loading of DCs may be a particularly good protocol for generating CTLs against self-antigens, which may not otherwise be considered good targets because of their low immunogenicity. We also show that HM1.24 may be an effective antigen for targeting MM.

Antigens, Neoplasm↗
PubMed2003

L-type voltage-gated calcium channel attends regulation of tyrosine phosphorylation of NMDA receptor subunit 2A induced by transient brain ischemia.

To study the mechanism of the L-type voltage-gated calcium channel (L-VGCC) involved in neuronal injury induced by brain ischemia and reperfusion (I/R), transient (15 min) brain ischemia was induced by four-vessel occlusion of Sprague-Dawley (SD) rats. Tyrosine phosphorylation of NR2A and interaction of NR2A with Src and Pyk2 in hippocampus induced by brain ischemia and reperfusion (I/R) were determined by immunoprecipitation and immunoblot(ting). Tyrosine phosphorylation of NR2A in hippocampus was enhanced after I/R. Interaction of NR2A with Src and Pyk2, tyrosine phosphorylation and kinase activity of Src and Pyk2 also increased after I/R. All the increases were partly inhibited by L-VGCC antagonist nifedipine administered to rats 20 min prior to brain ischemia. The results suggested that increase of tyrosine phosphorylation of NR2A induced by I/R had a relation to activation of L-VGCC. Src and Pyk2 interacting with NR2A might also be involved in this regulation of the tyrosine phosphorylation of NR2A induced by I/R.

Animals↗
PubMed2003

Ring-chain tautomerism in organic synthesis: synthesis of heterocyclic enamines from a novel and practical formal ring transformation reaction of lactones.

A novel approach to heterocyclic enamines has been developed from the formal ring transformation reaction of lactones. The synthesis comprises consecutive Reformatsky reaction of lactones and mesylation of the resulting mixture of ring-chain tautomers in a one-pot reaction, followed by cyclocondensation reaction with primary amines. The synthetic application of this method was demonstrated by a straightforward preparation of indolizidine compounds via N-(3-bromopropyl)-substituted enamine intermediates. The use of cheap and readily available materials and reagents under very mild conditions renders this formal ring transformation method practical and applicable in the preparation of various heterocyclic enamines that are the precursors for (poly)hydroxylated alkaloid derivatives.

Journal Article↗
PubMed2003

Construction of antisense transforming growth factor beta 1 gene and its effect on the proliferation by expression in osteosarcoma cells.

To construct the antisense transforming growth factor beta 1 (TGF beta 1) gene and investigate the effect of TGF beta 1 autocrine loop blockage on the proliferation of osteosarcoma cells. TGF beta 1 cDNA was cloned by RT-PCR from human osteosarcoma cells (MG-63) and inserted into pcDNA3 to construct an antisense expression vector, which was dubbed pcDNA3-TGF beta 1(-). MTT was used to detect the proliferation of osteosarcoma cells transfected by antisense TGF beta 1 gene. Our results showed that the proliferation of the transfected osteosarcoma cells was suppressed markedly. It is concluded that TGF beta 1 autocrine loop blockage in osteosarcoma cells could inhibit cell proliferation, which might be helpful for gene therapy of osteosarcoma.

Antisense Elements (Genetics)↗
PubMed2003

A genome sequence of novel SARS-CoV isolates: the genotype, GD-Ins29, leads to a hypothesis of viral transmission in South China.

We report a complete genomic sequence of rare isolates (minor genotype) of the SARS-CoV from SARS patients in Guangdong, China, where the first few cases emerged. The most striking discovery from the isolate is an extra 29-nucleotide sequence located at the nucleotide positions between 27,863 and 27,864 (referred to the complete sequence of BJ01) within an overlapped region composed of BGI-PUP5 (BGI-postulated uncharacterized protein 5) and BGI-PUP6 upstream of the N (nucleocapsid) protein. The discovery of this minor genotype, GD-Ins29, suggests a significant genetic event and differentiates it from the previously reported genotype, the dominant form among all sequenced SARS-CoV isolates. A 17-nt segment of this extra sequence is identical to a segment of the same size in two human mRNA sequences that may interfere with viral replication and transcription in the cytosol of the infected cells. It provides a new avenue for the exploration of the virus-host interaction in viral evolution, host pathogenesis, and vaccine development.

Base Sequence↗