Biomedical subjects

Ning Lu

Publications and source records attributed to Ning Lu.

At least 19 recordsLinked to original sources

PubMed2006

Tissue microarray analysis reveals a tight correlation between protein expression pattern and progression of esophageal squamous cell carcinoma.

BACKGROUND: The development of esophageal squamous cell carcinoma (ESCC) progresses a multistage process, collectively known as precursor lesions, also called dysplasia (DYS) and carcinoma in situ (CIS), subsequent invasive lesions and final metastasis. In this study, we are interested in investigating the expression of a variety of functional classes of proteins in ESCC and its precursor lesions and characterizing the correlation of these proteins with ESCC malignant progression. METHODS: Fas, FADD, caspase 8, CDC25B, fascin, CK14, CK4, annexin I, laminin-5gamma2 and SPARC were analyzed using immunohistochemistry on tissue microarray containing 205 ESCC and 173 adjacent precursor lesions as well as corresponding normal mucosa. To confirm the immunohistochemical results, three proteins, fascin, CK14 and laminin-5gamma2, which were overexpressed in ESCC on tissue microarray, were detected in 12 ESCC cell lines by Western blot assay. RESULTS: In ESCC and its precursor lesions, FADD, CDC25B, fascin, CK14, laminin-5gamma2 and SPARC were overexpressed, while Fas, caspase 8, CK4 and annexin I were underexpressed. The abnormalities of these proteins could be classified into different groups in relation to the stages of ESCC development. They were "early" corresponding to mild and moderate DYS with overexpression of fascin, FADD and CDC25B and underexpression of Fas, caspase 8, CK4 and annexin I, "intermediate" to severe DYS and CIS with overexpression of FADD and CK14, and "late" to invasive lesions (ESCC) and to advanced pTNM stage ESCC lesions with overexpression of CK14, laminin-5gamma2 and SPARC. CONCLUSION: Analyzing the protein expression patterns of Fas, FADD, caspase 8, CDC25B, fascin, CK14, CK4, annexin I, laminin-5gamma2 and SPARC would be valuable to develop rational strategies for early detection of lesions at risk in advance as well as for prevention and treatment of ESCC.

Adult↗

PubMed2006

Functional polymorphisms in FAS and FASL contribute to increased apoptosis of tumor infiltration lymphocytes and risk of breast cancer.

The FAS-FASL system plays crucial role in counterattack of cancer cell against immune system. This study examined the effects of FAS (-1377G/A and -670A/G) and FASL (-844T/C and 7896G/C) polymorphisms on breast cancer risk and apoptosis of T lymphocytes. The effect on breast cancer risk was determined by case-control analysis of 840 patients and 840 controls. The effects on T-lymphocyte apoptosis were determined by activation-induced cell death (AICD) of T cells ex vivo and by analyzing apoptotic tumor-infiltrating lymphocytes (TILs) in breast cancer tissue. We found moderately increased risk associated with FAS -1377AG [odds ratio (OR), 1.29; 95% confidence interval (CI), 1.05-1.59] and -1377AA (OR, 1.36; 95% CI, 1.01-1.82) genotypes compared with the -1377GG genotype and decreased risk associated with FASL -844CT (OR, 0.76; 95% CI, 0.62-0.94) and -844TT (OR, 0.66; 95% CI, 0.43-1.00) genotypes compared with the -844CC genotype. T lymphocytes with the FASL -844CC genotype had heightened FASL expression that is associated with increased AICD of the T cells stimulated by MCF-7 cells or phytohemagglutinin compared with the FASL -844TT genotype (10.38 +/- 4.09% and 24.29 +/- 1.50% versus 6.03 +/- 0.41% and 17.96 +/- 3.66%; P < 0.05 and 0.001). Breast cancer patients with the FASL -844CC genotype had higher apoptotic TILs in their cancer tissues than those with the FASL -844TT genotype (33.7 +/- 1.2% versus 19.1 +/- 2.0%; P = 0.007). These findings indicate that functional polymorphisms in FAS and FASL contribute to increased apoptosis of tumor infiltration lymphocytes and risk of breast cancer.

Adult↗

PubMed2006

Genome-wide loss of heterozygosity and copy number alteration in esophageal squamous cell carcinoma using the Affymetrix GeneChip Mapping 10 K array.

BACKGROUND: Esophageal squamous cell carcinoma (ESCC) is a common malignancy worldwide. Comprehensive genomic characterization of ESCC will further our understanding of the carcinogenesis process in this disease. RESULTS: Genome-wide detection of chromosomal changes was performed using the Affymetrix GeneChip 10 K single nucleotide polymorphism (SNP) array, including loss of heterozygosity (LOH) and copy number alterations (CNA), for 26 pairs of matched germ-line and micro-dissected tumor DNA samples. LOH regions were identified by two methods--using Affymetrix's genotype call software and using Affymetrix's copy number alteration tool (CNAT) software--and both approaches yielded similar results. Non-random LOH regions were found on 10 chromosomal arms (in decreasing order of frequency: 17p, 9p, 9q, 13q, 17q, 4q, 4p, 3p, 15q, and 5q), including 20 novel LOH regions (10 kb to 4.26 Mb). Fifteen CNA-loss regions (200 kb to 4.3 Mb) and 36 CNA-gain regions (200 kb to 9.3 Mb) were also identified. CONCLUSION: These studies demonstrate that the Affymetrix 10 K SNP chip is a valid platform to integrate analyses of LOH and CNA. The comprehensive knowledge gained from this analysis will enable improved strategies to prevent, diagnose, and treat ESCC.

Aged↗

PubMed2006

Clinical report of cervical arthroplasty in management of spondylotic myelopathy in Chinese.

OBJECTIVES: To investigate clinical effects and manual operational point of Bryan cervical disc prosthesis in Chinese, to observe the stability and range of movement (ROM) post-operatively. METHODS AND MATERIALS: From 2003,12 to 2005,12, Bryan disc prosthesis replacement applied in 83 cases (102 levels) of cervical spondylotic myelopathy (CSM) after anterior decompression in our hospital. Clinical (JOA grade and Odom's scale) and radiological (X-ray of flexion, extension; left and right bending position) follow-up was performed. Systemic radiographic study about stability and ROM of replaced level post operationally were measured. CT or MRI scans were applied in all cases to evaluate the signs of the prosthesis deflexion and hetero-ossification in the replaced levels. RESULTS: At least 12 months follow-up were done in 65/83 of these patients. All of 83 patients were improved according to Odsm's scale. JOA score increased from average 8.7 to 15.5. There was no prosthesis subsidence. Replaced segment achieved stability and restored partial of normal ROM 4.73 degrees (3.7 degrees -5.9 degrees ) early postoperation and 8.12 degrees (5.8 degrees -13.6 degrees ) more than 12 months postoperation in flex and extension position. No obvious loss of lordosis was found. CT or MRI follow-up shows position deflexion of the prosthesis metal endplates (<1.5 mm) in 14/77 levels and (1.5-3 mm) in 4/77. heter-ossification was found in the replaced levels only in 2 cases. CONCLUSION: Byran cervical disc prosthesis restored motion to the level of the intact segment in flexion-extension and lateral bending in post-operative images. At the same time, it can achieve good anterior decompression treatment effect and immediate stability in replaced 1 or 2 levels, and which is a new choice for the treatment of CSM.

Journal Article↗

PubMed2006

No association between HPV infection and the neoplastic progression of esophageal squamous cell carcinoma: result from a cross-sectional study in a high-risk region of China.

Esophageal cancer is a leading cause of cancer death, especially in developing countries. In high-risk regions, squamous cell carcinoma is the most common type of esophageal cancer, and its etiology remains poorly understood. The purpose of this study was to evaluate the association between human papillomavirus (HPV) infection and esophageal squamous cell carcinoma (ESCC) and related precursor lesions in a high-risk area of China. We conducted a cross-sectional study among adult inhabitants of Linxian, China. All subjects were interviewed about potential risk factors, had the length of their esophagus sampled by a balloon cytology examination and underwent endoscopy with mucosal iodine staining and biopsy of all unstained lesions. A multivalent HPV hybridization probe, Digene Hybrid Capture II (Gaithersburg, MD), which recognizes high-risk types 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59 and 68, was used to determine the HPV infection status of the cytologic specimens, and the endoscopic biopsies were used to classify each subject's esophageal disease. 740 subjects completed the cytologic and endoscopic exams, and 702 had adequate cytologic and biopsy specimens. Using a cutpoint of > or =3.0 pg/ml of HPV DNA to define a positive test, HPV positivity was identified in 13% (61/475) of subjects without squamous dysplasia, 8% (8/102) with mild dysplasia, 7% (6/83) with moderate dysplasia, 16% (6/38) with severe dysplasia and zero (0/4) with invasive ESCC. Changing the cutpoint defining a positive test did not change the association of HPV infection and dysplasia grade. In this high-risk population, infection of esophageal cells with high-risk HPV types occurs in 13% of asymptomatic adults with no evidence of squamous dysplasia and a similar proportion of individuals with mild, moderate or severe dysplasia. This suggests that HPV infection is not a major risk factor for ESCC in this high-risk Chinese population. Further studies are warranted to determine if infection with this agent is associated with neoplastic progression in a subset of cases.

Adult↗

PubMed2006

Reduced MTA1 expression by RNAi inhibits in vitro invasion and migration of esophageal squamous cell carcinoma cell line.

To distinguish aggressive esophageal squamous cell carcinoma from indolent disease is the important clinical challenge. Studies have indicated that metastasis-associated gene 1(Mta1) played a role in the process of metastasis of carcinoma. The overexpression of Mta1 gene has been found in a variety of tumors. To identify the detailed roles of MTA1 protein in the carcinogenesis of esophageal squamous cell carcinoma, this study analyzed the pathological specimens on tissue microarray derived from 72 patients using immunohistochemistry. MTA1 expression increased in the nuclear with the development of esophageal squamous cell carcinoma from normal epithelial cell, dysplasia, to invasive cancer. In biological studies with human esophageal squamous cell carcinoma cell line, MTA1 plays its roles to promote cancer cell invasion, adhesion and movement. RNA interference (RNAi) against MTA1 decreased the malignant phenotypes. Gene microarray analysis revealed some metastasis-associated genes were altered by MTA1 RNAi. This study started an effective beginning to explore metastasis mechanisms and cancer gene therapy strategy targeting MTA1.

Base Sequence↗

PubMed2006

CD147 overexpression on synoviocytes in rheumatoid arthritis enhances matrix metalloproteinase production and invasiveness of synoviocytes.

Macrophage-like synoviocytes and fibroblast-like synoviocytes (FLS) are known as the most active cells of rheumatoid arthritis (RA) and are close to the articular cartilage in a position enabling them to invade the cartilage. Macrophage-like synoviocytes and FLS expression of matrix metalloproteinases (MMPs) and their interaction has aroused great interest. The present article studied the expression of CD147, also called extracellular matrix metalloproteinase inducer, on monocytes/macrophages and FLS from RA patients and its potential role in enhancing MMPs and the invasiveness of synoviocytes. Expression of CD147 on FLS derived from RA patients and from osteoarthritis patients, and expression of CD147 on monocytes/macrophages from rheumatic synovial fluid and healthy peripheral blood were analyzed by flow cytometry. The levels of CD147, MMP-2 and MMP-9 mRNA in FLS were detected by RT-PCR. The role of CD147 in MMP production and the cells' invasiveness in vitro were studied by the co-culture of FLS with the human THP-1 cell line or monocytes/macrophages, by gel zymography and by invasion assay. The results showed that the expression of CD147 was higher on RA FLS than on osteoarthritis FLS and was higher on monocytes/macrophages from rheumatic synovial fluid than on monocytes/macrophages from healthy peripheral blood. RT-PCR showed that the expressions of CD147, MMP-2 and MMP-9 mRNA was higher in RA FLS than in osteoarthritis FLS. A significantly elevated secretion and activation of MMP-2 and MMP-9 were observed in RA FLS co-cultured with differentiated THP-1 cells or RA synovial monocytes/macrophages, compared with those co-cultured with undifferentiated THP-1 cells or healthy control peripheral blood monocytes. Invasion assays showed an increased number of invading cells in the co-cultured RA FLS with differentiated THP-1 cells or RA synovial monocytes/macrophages. CD147 antagonistic peptide inhibited the MMP production and the invasive potential. Our studies demonstrated that the CD147 overexpression on monocytes/macrophages and FLS in RA patients may be responsible for the enhanced MMP secretion and activation and for the invasiveness of synoviocytes. These findings suggest that CD147 may be one of the important factors in progressive joint destruction of RA and that CD147 may be a potential therapeutic target in RA treatment.

Adult↗

PubMed2006

Radiotherapy as primary treatment for stage IE and IIE nasal natural killer/T-cell lymphoma.

UNLABELLED: PURPOSE The optimal therapy remains unclear for nasal natural killer (NK)/T-cell lymphoma. The purpose of this study is to analyze the outcome of radiotherapy as the primary treatment for localized stage IE and IIE diseases. PATIENTS AND METHODS: One hundred five patient cases were reviewed. There were 83 stage IE and 22 stage IIE patients. All except three patients received radiotherapy (RT) alone or RT combined with chemotherapy (CT; combined-modality therapy [CMT]). Overall, 31 patients were treated with RT alone, 34 with RT followed by CT, 37 with CT followed by RT, and three with CT alone. RESULTS: Five-year overall survival (OS) and progression-free survival (PFS) for all patients were 71% and 59%, respectively. The 5-year OS and PFS were 78% and 63% for stage IE, and 46% and 40% for stage IIE, respectively. Complete response (CR) was achieved in 91 patients (87%) after RT and/or CT. Initial RT resulted in a superior CR as compared with initial CT, with 54 (83%) of 65 patients achieving CR with initial RT, versus only eight (20%) of 40 after initial CT. For 102 patients who received RT with or without CT, the outcome of primary treatment with RT alone was compared with that of CMT. Five-year OS and PFS was 66% and 61% for RT alone, and 76% and 61%% for CMT, respectively (OS, P = .6433; PFS, P = .8391). CONCLUSION: RT as primary therapy resulted in good outcome in early-stage disease, and the addition of CT to RT was not accompanied by an improvement in survival.

Adolescent↗

PubMed2006

Magic structures of h-passivated 110 silicon nanowires.

We report a genetic algorithm approach combined with ab initio calculations to determine the structure of hydrogenated 110 Si nanowires. As the number of atoms per length increases, we find that the cross section of the nanowire evolves from chains of six-atom rings to fused pairs of such chains to hexagons bounded by {001} and {111} facets. Our calculations predict that hexagonal wires become stable starting at about 1.2 nm diameter, which is consistent with recent experimental reports of nanowires with diameters of about 3 nm.

Hydrogen↗

PubMed2006

Effect of epitope position on neutralization by anti-human immunodeficiency virus monoclonal antibody 2F5.

The membrane-proximal region of the human immunodeficiency virus type 1 (HIV-1) transmembrane protein (TM) is critical for envelope (Env)-mediated membrane fusion and contains the target for broadly reactive neutralizing antibody 2F5. It has been proposed that 2F5 neutralization might involve interaction of its long, hydrophobic, complementarity-determining region (CDR) H3, with adjacent viral membrane. Using Moloney murine leukemia virus (MLV) as a tool, we examined the effect of epitope position on 2F5 neutralization. When the 2F5 epitope was inserted in the proline-rich region of MLV Env surface protein (SU), 2F5 blocked cell fusion and virus infection, whereas MLV with a hemagglutinin (HA) epitope at the same position was not neutralized by anti-HA, even though the antibodies bound their respective Envs on the surface of infected cells and viruses equally well. When the 2F5 epitope was inserted in the MLV Env TM at a position comparable to its natural position in HIV-1 TM, 2F5 antibody blocked Env-mediated cell fusion. Epitope position had subtle effects on neutralization by 2F5: the antibody concentration for 50% inhibition of cell fusion was more than 10-fold lower when the 2F5 epitope was in SU than in TM, and inhibition was less complete at high concentrations of antibody; we discuss possible explanations for these effects of epitope position. Since membrane proximity was not required for neutralization by 2F5 antibody, we speculate that the CDR H3 of 2F5 contributes to neutralization by destabilizing an adjacent protein rather than by inserting into an adjacent membrane.

Antibodies, Monoclonal↗

PubMed2006

[Effects of PMA on CD147 expression in cultured THP-1 cells and monocytes of RA patients].

AIM: To investigate the expression of CD147 both on cellular membrane and in culture supernatant of in vitro cultured THP-1 cells and monocytes of RA patients before and after stimulation with phorbol myristate acetate (PMA). METHODS: Human peripheral blood monocytes (HPBMs) were segregated from RA patients by adherent culture method. After the HPBMs and THP-1 cells were stimulated with PMA, the expression rate and expression intensity of CD147 on THP-1 cells and HPBMs of RA patients were determined by flow cytometry. The soluble CD147 levels in culture supernatant of in vitro cultured THP-1 cells and HPBMs were quantified by double antibody Sandwich ELISA. RESULTS: The soluble CD147 in the supernatant of cultured THP-1 cells and HPBMs was detectable before PMA stimulation. Both cells showed high CD147 expression. After PMA stimulation, soluble CD147 level in the supernatant of THP-1 cells increased. CD147 expression on THP-1 cells firstly increased then decreased and kept stable for several days. CD147 expression on HPBMs of RA patients decreased, but CD147 level in the culture supernatant of HPBMs of RA patients increased and kept stable for 2 days. CONCLUSION: CD147 molecule can be shed from the membrane of THP-1 cells and HPBMs of RA patients, or it can be directly secreted into the culture supernatant from the two kinds of cells. PMA can up-regulate the level of soluble CD147.

Arthritis, Rheumatoid↗

PubMed2006

[Preliminary report of Nd: YAG laser embolysis for branch retinal artery occlusion].

OBJECTIVE: In this study, the clinical effect of the Nd: YAG laser embolysis on branch retinal artery occlusion was evaluated. METHODS: A fundus contact lens was used to focus the Nd: YAG laser on the embolus within the retinal arteriole. 0.8 to 0.9 mJ of laser pulse was delivered directly to the embolus. Fundus photographs were taken before and immediately after the treatment. Follow-up time ranged from 2 weeks to 4 months, average about 7 weeks. Seven cases received the treatment, including 5 male and 2 female patients. Age of those cases ranged from 49 to 73, average 61 years. The duration of the disease ranged from 1 to 60 days, average 13 days. RESULTS: Before treatment, visual acuity ranged from 0.06 to 0.8. Embolus can be detected in all the 7 cases. After treatment, all the cases showed immediate recovery of blood flow in the occluded arteriole both in fundus examination and fundus fluorescein angiography. The vision in the patients was improved in the follow-up. Visual acuity ranged from 0.2 approximately 1.0. In most cases, visual field defect still existed in the ischemic area. Complications included local retinal hemorrhages in some cases and vitreous hemorrhage, but those hemorrhages were gradually absorbed and did not affect the final visual prognosis. CONCLUSIONS: Nd: YAG laser embolysis for branch retinal artery occlusion is an effective treatment and the treatment is relatively safe.

Aged↗

PubMed2006

[Long-term follow-up study of nonischemic central retinal vein occlusion].

OBJECTIVE: To explore the clinical characteristic, visual prognosis and related factors of nonischemic central vein occlusion. METHODS: Retrospective data analysis (including visual acuity, color fundus photography and fundus fluorescein angiography) was conducted in patients with nonischemic CRVO who were followed-up for 3 years or longer. RESULTS: The data of 35 cases (37 eyes) were analyzed. The follow-up time was 3 - 15 years, averaged 4.5 years. Age of those patients ranged from 18 to 76 years, averaged 56 years. Thirty cases (32 eyes) were over 40 years old. Two cases had chronic angle closure glaucoma. At the final visit, visual acuity improved in only 2 eyes (5%), remained the same in 11 eyes (30%), and decreased in 24 eyes (65%). Twenty-eight eyes (75%) had a final visual acuity of 20/200 or less. Nine eyes (24%) transformed to the ischemic type, among which neovascular glaucoma occurred in 5 eyes. Macular complications were the major causes of serious visual impairment. The patients with chronic angle closure glaucoma and partial optic nerve atrophy had relatively good final visual acuity. CONCLUSIONS: Nonischemic CRVO can cause severe visual impairment. Macular complications are the major causes of vision loss. Partial optic nerve atrophy may have a protective effect on visual acuity in CRVO.

Adolescent↗

PubMed2005

Tandem Sp1/Sp3 sites together with an Ets-1 site cooperate to mediate alpha11 integrin chain expression in mesenchymal cells.

Alpha11beta1 integrin is a collagen receptor, which is expressed in a highly regulated manner in a specific subset of ectomesenchymally and mesodermally derived cells. We previously established that a 3 kb region upstream of the transcription start site of the ITGA11 gene efficiently induced alpha11 transcription in a cell-type specific manner. Using the human fibrosarcoma cell line HT1080 and human skin fibroblasts, we now report that the majority of the activity in the proximal promoter resides in a region spanning nt +25 to nt -176. Mutation and deletion analyses using luciferase reporter assays showed that tandem low affinity Sp1/Sp3 binding sites, together with an Ets-1-like binding site, were needed for the proximal promoter activity in mesenchymal cells. EMSAs and supershift assays showed that Sp1 and Sp3 both bind to the Sp1/Sp3 binding sites, whereas occupation of the Ets-1 binding site appears to be Sp3-dependent. Chromatin immunoprecipitation assays verified that Sp1, Sp3 and Ets-1 can bind the promoter in vivo. In heterologous Drosophila SL2 cells, Sp1, Sp3 and Ets-1 all transactivated the alpha11 promoter, with Sp1 being the most efficient activator. The lack of any synergistic effect of Sp1/Sp3 and Ets-1 in SL2 cells indicates that an Ets family member other than Ets-1 might be involved in regulating alpha11 transcription in mesenchymal cells. The central role of Sp1 in regulating alpha11 RNA transcription was further verified by the ability of the Sp1 inhibitor mithramycin A to efficiently attenuate alpha11 RNA and protein levels in primary fibroblasts. The proximal promoter itself was able to confer cell-type specific transcription on HT1080 cells and embryonic fibroblasts but not on U2OS and JAR cells. We speculate that the "mesenchymal signature" of alpha11 integrin gene expression is controlled by the activity of Sp1/Sp3, fibroblast-specific combinations of Ets family members and yet unidentified enhancer-binding transcription factors.

Animals↗

PubMed2005

Overexpression of EB1 in human esophageal squamous cell carcinoma (ESCC) may promote cellular growth by activating beta-catenin/TCF pathway.

Esophageal squamous cell carcinoma (ESCC) has a multifactorial etiology involving environmental and/or genetic factors. End-binding protein 1 (EB1), which was cloned as an interacting partner of the adenomatous polyposis coli (APC) tumor suppressor protein, was previously found overexpressed in ESCC. However, the precise role of EB1 in the development of this malignancy has not yet been elucidated. In this study, we analysed freshly resected ESCC specimens and demonstrated that EB1 was overexpressed in approximately 63% of tumor samples compared to matched normal tissue. We report that overexpression of EB1 in the ESCC line EC9706 significantly promotes cell growth, whereas suppression of EB1 protein level by RNA interference significantly inhibited growth of esophageal tumor cells. In addition, EB1 overexpression induced nuclear accumulation of beta-catenin and promoted the transcriptional activity of beta-catenin/T-cell factor (TCF). These effects were partially or completely abolished by coexpression of APC or DeltaN TCF4, respectively. Also, we found that EB1 affected the interaction between beta-catenin and APC. Furthermore, EB1 overexpression was correlated with cytoplasmic/nuclear accumulation of beta-catenin in primary human ESCC. Taken together, these results support the novel hypothesis that EB1 overexpression may play a role in the development of ESCC by affecting APC function and activating the beta-catenin/TCF pathway.

Base Sequence↗

PubMed2005

Central angiotensin II-enhanced splenic cytokine gene expression is mediated by the sympathetic nervous system.

We tested the hypothesis that central angiotensin II (ANG II) administration would activate splenic sympathetic nerve discharge (SND), which in turn would alter splenic cytokine gene expression. Experiments were completed in sinoaortic nerve-lesioned, urethane-chloralose-anesthetized, splenic nerve-intact (splenic-intact) and splenic nerve-lesioned (splenic-denervated) Sprague-Dawley rats. Splenic cytokine gene expression was determined using gene-array and real-time RT-PCR analyses. Splenic SND was significantly increased after intracerebroventricular administration of ANG II (150 ng/kg, 10 microl), but not artificial cerebrospinal fluid (aCSF). Splenic mRNA expression of IL-1beta, IL-6, IL-2, and IL-16 genes was increased in ANG II-treated splenic-intact rats compared with aCSF-treated splenic-intact rats. Splenic IL-1beta, IL-2, and IL-6 gene expression responses to ANG II were significantly reduced in splenic-denervated compared with splenic-intact rats. Splenic gene expression responses did not differ significantly in ANG II-treated splenic-denervated and aCSF-treated splenic-intact rats. Splenic blood flow responses to intracerebroventricular ANG II administration did not differ between splenic-intact and splenic-denervated rats. These results provide experimental support for the hypothesis that ANG II modulates the immune system through activation of splenic SND, suggesting a novel relation between ANG II, efferent sympathetic nerve outflow, and splenic cytokine gene expression.

Angiotensin II↗

PubMed2005

Involvement of CD147 in overexpression of MMP-2 and MMP-9 and enhancement of invasive potential of PMA-differentiated THP-1.

BACKGROUND: During infection and inflammation, circulating blood monocytes migrate from the intravascular compartments to the extravascular compartments, where they mature into tissue macrophages. The maturation process prepares the cells to actively participate in the inflammatory and immune responses, and many factors have been reported to be involved in the process. We found in our study that CD147 played a very important role in this process. RESULTS: By using PMA-differentiated human monocyte cells line THP-1, we found that CD147 mediated matrix metalloproteinases (MMPs) expression of the leukemic THP-1 cells and thus enhanced the invasiveness of THP-1 cells. After 24 hours of PMA-induced monocyte differentiation, the mean fluorescence intensity of CD147 in differentiated THP-1 cells (289.61 +/- 31.63) was higher than that of the undifferentiated THP-1 cells (205.1 +/- 19.25). There was a significant increase of the levels of proMMP-2, proMMP-9 and their activated forms in the differentiated THP-1 cells. Invasion assays using reconstituted basement membrane showed a good correlation between the invasiveness of THP-1 cells and the production of MMP-2 and MMP-9. The difference in the MMPs expression and the invasive ability was significantly blocked by HAb18G/CD147 antagonistic peptide AP-9. The inhibitory rate of the secretion of proMMP-9 in the undifferentiated THP-1 cells was 45.07%. The inhibitory rate of the secretion of proMMP-9, the activated MMP-9 and proMMP-2 in the differentiated THP-1 cells was 52.90%, 53.79% and 47.80%, respectively. The inhibitory rate of invasive potential in the undifferentiated cells and the differentiated THP-1 cells was 41.82 % and 25.15%, respectively. CONCLUSION: The results suggest that the expression of CD147 is upregulated during the differentiation of monocyte THP-1 cells to macrophage cells, and CD147 induces the secretion and activation of MMP-2 and MMP-9 and enhances the invasive ability of THP-1 cells. The matured monocytes / macrophages, via their high expression of CD147, may play an important role in promoting the tissue repair or tissue damage during their inflammatory response.

Basigin↗

PubMed2005

Overexpression of human pituitary tumor transforming gene (hPTTG), is regulated by beta-catenin /TCF pathway in human esophageal squamous cell carcinoma.

Overexpression of human pituitary tumor transforming gene (PTTG) is wildly detected in many tumors, including esophageal cancer. Besides overexpression of PTTG in esophageal squamous cell carcinoma (ESCC) tissues and cells, we detected accumulation of cytoplasmic beta-catenin in ESCC. In our study, a putative TCF4-binding element (TBE) was identified in PTTG promoter region. The activity of PTTG promoter containing the TBE was activated by S37Abeta-catenin and inhibited by dominant-negative TCF. Furthermore, the activation by S37Abeta-catenin was mostly abrogated among PTTG promoter region without the TBE or with a mutant one. By using biotin-streptavidin pull-down assay, we also found that the TBE among PTTG promoter bound to TCF-4 protein. Moreover, levels of PTTG mRNA and protein were increased by S37Abeta-catenin. Finally, it is noticeable that we detected a correlation between beta-catenin localization and PTTG expression in 69 primary ESCC (p<0.01). In brief, our study shows that overexpression of PTTG in ESCC is likely due to the activation of beta-catenin/WNT signaling. As a target gene of beta-catenin/TCF pathway, PTTG may play an important role in tumorigenesis of human ESCC.

Base Sequence↗