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Biomedical subjects

Xiang Guo

Publications and source records attributed to Xiang Guo.

31 records · Page 2Linked to original sources
PubMed2004

Characterization of a new SNP c767A/T (Arg222Trp) in the candidate TSG FUS2 on human chromosome 3p21.3: prevalence in Asian populations and analysis of association with nasopharyngeal cancer.

The FUS2 gene, encoding a novel cytoplasmic acetyltransferase, resides in the tumor suppressor gene region on human chromosome 3p21.3 and is considered a promising candidate tumor suppressor gene. We have identified a new single nucleotide polymorphism (SNP), c767A/T, in the coding region of the gene. The polymorphism leads to a non-conservative amino acid change (R222W) located between the acetyltransferase (GNAT) and the proline-rich domains of the protein. We have analyzed 254 subjects included in 14 sub-populations. The occurrence of the SNP varies with the ethnicity of the population, suggesting that this SNP could be a valuable biomarker for population genetics. It is most prevalent in various Asian populations (T allele frequency>0.54), followed by the Canadian polar Inuit (T allele frequency=0.3), African American (T allele frequency=0.17), and Caucasian population (T allele frequency=0.1). Since nasopharyngeal carcinoma (NPC) is frequent in Southern China, Taiwan, Borneo and polar Canada, we further tested for the possible association of the FUS2 SNP with this form of endemic cancer. Our analysis, albeit limited, suggests no likely association between NPC and the FUS2 gene polymorphism. Further large-scale case-control studies are necessary and warranted to prove the strength of this contention.

Acetyltransferases↗
PubMed2004

Fos expression in the rat brain after intraperitoneal injection of Staphylococcus enterotoxin B and the effect of vagotomy.

The current study was designed to locate the neuronal activation in rat brain following intraperitoneal injection of Staphylococcus enterotoxin B (SEB) and observe the consequence of preliminary subdiaphragmatic vagotomy on SEB-induced brain Fos expression to clarify the role of the vagus nerve in sensation and transmission of abdominal SEB stimulation. The results showed that intraperitoneal SEB (1 mg/kg) induced a robust Fos expression in widespread brain areas. A significant increase of Fos immunoreactive cells were observed in the solitary tract nucleus, locus ceruleus, lateral parabrachial nucleus, ventrolateral part of central gray, medial amygdaloid nucleus, central amygdaloid nucleus, ventromedial part of thalamus, dorsomedial part of thalamus, hypothalamic paraventricular nucleus, lateral habenula, and lateral septum nucleus following SEB challenge. In hypothalamic paraventricular nucleus, in addition to the dense Fos expression in the parvocellular portion, some Fos-positive cells were also observed in the anterior magnocellular nucleus of the complex. Double immunofluorescence studies showed that these Fos-immunoreactive cells were mostly oxytocinergic. The results also showed that subdiaphragmatic vagotomy largely attenuated, but not totally abrogated, the brain Fos expression induced by abdominal administration of SEB. Our data suggest that peripheral SEB stimulation can induce activation of neurons in widespread brain areas and that the vagus plays a crucial role in transmitting the signal of abdominal immune stimulation to the brain.

Animals↗
PubMed2004

[Expression of topoisomerase IIalpha in nasopharyngeal carcinoma and its clinical significance].

BACKGROUND & OBJECTIVE: TopoisomeraseIIalpha (TopoIIalpha) is a protein in eukaryotic cell with many different roles in DNA duplication and repair. It was reported that the expression level of TopoIIalpha was related to the prognosis of many malignant tumors. The aim of this study was to investigate the relationship of expression of TopoIIalpha in nasopharyngeal carcinoma (NPC) with clinicopathologic factors and its prognostic significance. METHODS: The expression of TopoIIalpha was observed in 114 NPC cases using immunohistochemical staining. All of the patients were divided into two groups according to the expression level of TopoIIalpha. Kaplan-Meier survival analysis was used to analyze the relationship of expression of TopoIIalpha with recurrence and metastasis of tumor after radiotherapy. Cox proportional hazards model analysis was used to analyze the factors related to local recurrence of tumor. RESULTS: The expression of TopoIIalpha in NPC cells ranged from 0 to 90%; the average percentage was (22.63+/-21.92)%. The positive rate of TopoIIalpha was 43.9% (50/114) when 20% was used as the cut-off point. The positive rate of TopoIIalpha was not related to the sex, age, pathological type, and clinical staging. The 3-year relapse-free survival rates of negative group and positive group were 93.1% and 74.3%, respectively (P=0.0027). The 3-year disease-free survival rates of the two groups were 77.9% and 58.9%, respectively (P=0.0091). The metastasis-free survival rates of the two groups were 81.1% and 77.6%, respectively (P=0.566). Cox proportional hazards model analysis showed that the local recurrence of tumor was independently affected by the expression of TopoIIalpha. CONCLUSION: There is a high expression level of TopoIIalpha in a part of NPC.NPC patients with high expression of TopoIIalpha have a higher local recurrence rate and worse prognosis.

Adolescent↗
PubMed2004

[Phase I study of capecitabine with concurrent radiotherapy in early-stage nasopharyngeal carcinoma].

OBJECTIVE: To evaluate the dose-limiting toxicity (DLT), efficacy and maximum tolerated dose (MTD) of capecitabine with concurrent radiotherapy in patients with node-positive stage II nasopharyngeal cancer. METHODS: From August 2002 to June 2003, 30 patients with node-positive stage II T(2)N(1)M(0) nasopharyngeal cancer were retrospectively reviewed. Median age 43 years (range 32 - 63 years), ECOG performance status <or= 2. Radiotherapy of 68 - 72 Gy/34 - 36 fractions was delivered to the nasopharynx and 64 - 70 Gy/32 - 35 fractions to the node-positive area. Capecitabine was administered orally on day 1 of radiotherapy by an intermittent schedule (14 days treatment; 7-day rest) at 3 weekly intervals for two cycles. Patients were alloted into one of four escalating dose cohorts (500, 750, 1000 and 1250 mg/m(2), bid). Dose escalation was done after six patients had completed 2 cycles of chemotherapy at the previous dose level with DLT assessed. RESULTS: Twenty-eight patients were evaluable for toxicity and efficacy: CR 12 (42.9%), PR 13 (46.4%), SD 3 (10.7%), the overall response rate (CR + PR) was 89.3%. The CR response rate of the node-positive area and of the nasopharynx were 50.0% (14/28) and 46.4% (13/28). No DLT was observed at the dosage group of 500 mg/m(2) and 750 mg/m(2). Three of 9 patients experienced DLT at 1000 mg/m(2) with grade III stomatitis; 4 of 6 at 1250 mg/m(2) with grade III stomatitis (4/6), grade III diarrhea with grade IV febrile neutropenia (1/6) and grade III thrombocytopenia (1/6). The toxicity of grade I and II was hand-foot syndrome (4/28), fatigue (14/28), nausea and vomiting (19/28), diarrhea (5/27), and weight loss (21/28). CONCLUSION: A dose of 750 mg/m(2) of capecitabine might be recommended for combination with radiotherapy. This regimen is tolerable and valid for nasopharyngeal carcinoma. A randomised phase III comparison with 5-Fu is justified.

Adult↗
PubMed2004

Combined genetic and transcriptional profiling of acute myeloid leukemia with normal and complex karyotypes.

BACKGROUND AND OBJECTIVES: Acute myeloid leukemia (AML) is a heterogeneous group of diseases. Patients with a normal karyotype constitute the largest single group; multiple chromosome rearrangements involving three or more chromosomes occur in 5 10% of AML patients. The pathophysiologic mechanisms underlying both groups are largely unknown. In the current study, we have systematically combined transcriptional profiles with cytogenetic data from 15 AML patients with either normal or complex karyotypes. DESIGN AND METHODS: The expression profiles were investigated by unsupervised hierarchical clustering, supervised cluster analysis, and comparative genomic microarray analysis. In addition, the samples were analyzed by G-banding and/or spectral karyotyping and comparative genomic hybridization. RESULTS: Our results show that AML with complex karyotypes exhibit a gene expression profile that is specific to this group of patients. The differentially expressed genes included several located on 5q and 7q, as well as genes involved in controlling cell division. We also found that DNA gains and losses caused by multiple chromosome rearrangements result in altered gene expression in a gene-dosage-dependent manner. INTERPRETATION AND CONCLUSIONS: These data provide insight into the mechanisms of multiple chromosome rearrangements and further demonstrate that the expression patterns of AML are strongly linked to the karyotypic status, even for the relatively undefined cytogenetic subgroup AML with complex karyotype.

Acute Disease↗
PubMed2004

[Clinical value of vascular endothelial growth factor detection in forecasting distant metastasis risk of nasopharyngeal carcinoma].

BACKGROUND & OBJECTIVE: Vascular endothelial growth factor (VEGF)closely relates with the malignancy and metastasis of various kinds of cancers. This study was designed to evaluate the value of VEGF detection in forecasting distant metastasis risk of nasopharyngeal carcinoma(NPC)patients. METHODS: Tumor biopsies,and serum specimens were collected before treatment from 59 pathologically diagnosed NPC patients, hospitalized in our hospital from Mar. 1999 to Feb. 2000. Immunohistochemistry LSAB method was used to detect VEGF in NPC tissues. VEGF in NPC serum was detected by quantitative enzyme-linked immunosorbent assay (ELISA) method. Through follow-up study, the relationship between VEGF and distant metastasis of NPC patients was observed. RESULTS: The expression of VEGF in NPC tissue,and serum positively related with the distant metastasis (P< 0.05). Non-distant metastasis survival rates of different tissue VEGF groups were 100%(-), 95.24%(+), 65.19%(++), and 58.93%(+++), significant difference existed between every 2 groups (P=0.019 3). Non-distant metastasis survival rates of different serum VEGF groups were 82.57% (< 466.78 ng/L), and 59.11% (>/=466.78 ng/L)(P=0.021 1). Multi-prognostic factors analysis showed that VEGF expression in NPC tissue and serum had significant effects on distant metastasis of NPC. CONCLUSIONS: The detection of VEGF either in NPC tissue or in serum could be regarded as a valuable indicator for predicting distant metastasis risk of NPC patients. Combined detection of them could increase the chances of forcasting distant metastasis in NPC patients.

Adult↗
PubMed2003

[Significance of cell-free Epstein-Barr virus DNA in monitoring prognosis of nasopharyngeal carcinoma].

BACKGROUND & OBJECTIVE: It has been reported that cell-free Epstein-Barr virus (EBV-DNA) in plasma was useful in diagnosing and monitoring nasopharyngeal carcinoma (NPC). The current study was designed to evaluate the significance of EBV-DNA in monitoring the prognosis of nasopharyngeal carcinoma and to compare with VCA/IgA and EA/IgA. METHODS: EBV-DNA, VCA/IgA, and EA/IgA levels in plasma were detected in different NPC patients after radiotherapy, including 30 distant metastasis patients, 22 locoregional recurrence patients, 24 remission individuals who had been followed up more than 2 years after treatment. EBV-DNA was detected using real-time quantitative PCR system;VCA/IgA and EA/IgA were tested using regular immunofluorescence. In cohort study, the indexes were tested in different radiation periods for the 20 new cases of nasopharyngeal carcinoma. RESULTS: The median plasma EBV-DNA concentration was 135,100 copies/ml (interquartile range: 5,525-1,003,750) in metastasis group, 20,500 copies/ml (interquartile range: 0-58,500) in locoregional recurrence group and 0 copies/ml (interquartile range: 0-0) in continuous remission group (P< 0.05). The levels of VCA/IgA and EA/IgA had no significant difference in different groups. The high level of EBV-DNA concentration in metastasis group was more than that in locoregional recurrence group. At the level of 1,000,000 copies/ml, EBV DNA indicated distant metastasis of NPC with a specificity of 100% and a sensitivity of 27.3%; however, the sensitivity was 0 copies/ml in locoregional recurrence group. For the 20 new patients, EBV DNA concentration gradually decreased in the radiation period, 32,050 copies/ml (interquartile range: 3,880-317,750) before radiation, 0 copies/ml (interquartile range: 0-14,375) when 40 Gy radiation dose and 0 copies/ml (interquartile range: 0-2940) when the radiation finished (P< 0.05). However, the levels of VCA/IgA and EA/IgA had no significant difference. CONCLUSION: The plasma cell-free EBV-DNA is more valuable than VCA/IgA and EA/IgA for monitoring the prognosis of NPC patients.

Antigens, Viral↗
PubMed2003

[Construction and expression of prokaryotic expression vector of GAP-43 and preparation of monoclonal antibody against GAP-43].

AIM: To express the growth-associated protein-43 (GAP-43)in prokaryotic cells and prepare monoclonal antibody( mAb)against GAP-43. METHODS: Full length sequence of GAP-43 gene was amplified from the plasmid containing pGAP-43cDNA and was cloned into the expression vector pGEX-4T-I.GST-GAP-43 fusion protein was expressed in E. coil under IPTG induction. Expressed fusion protein was purified by glutathine agarose chromagraphy, Using purified protein as an immunogen, mAb against GAP-43 was prepared. RESULTS: The recombinant plasmid containing the target gene was constructed successfully. The fusion protein was expressed in E. coli in soluble form. The titer of anti-GAP-43mAb in ascites was 1: 10'. The Ig subclass and subtype of the mAb was IgG2a and K type, respectively. Specificity of the mAb was confirmed by ELISA, Western blot and immunofluorescence technique. CONCLUSION: The anti-GAP-43 mAb obtained has strong specificity and high titer, which provides an useful reagent for further studying the function of GAP-43 in nervous system.

Animals↗
PubMed2002

Experimental measurement of wind-sand flux and sand transport for naturally mixed sands.

This article presents an experimental test and a program to empirically fit experimental data for the horizontal flux of wind-blown sand passing through a unit area along a vertical direction per unit time. The experimental data for the sand flow flux as a function of the height for naturally mixed sands, which were chosen from a sand dune at the southeastern edge of the Tengger desert, were measured with a sand collector in a field wind tunnel. On the basis of the experimental data and a least squares method, a fitting program is proposed here and, further, an explicit form of an empirical formula varying with height and axial wind velocity or friction velocity for the flux structure of the sands is gained. After that, we obtain an explicit form of the empirical equation for the measurement of streamwise sand transport per unit width and unit time by integrating the empirical formula for sand flux along the height direction and considering the contribution of sand creep. Finally, we evaluate the effectiveness of the predictions of some equations, especially the well-known Bagnold equation and Kawamura equation, for predicting streamwise wind-sand transport using the empirical equation obtained for mixed sands. The results show that the predictions from Bagnold's equation in the region of friction velocity u(*)>0.47 m/s and Kawamura's equation in the region u(*t)<or=u(*)<0.35 m/s are effective. Meanwhile, the measurement results given from the empirical equation smoothly transit from Kawamura's prediction to Bagnold's prediction as the friction velocity increases in the range 0.35 m/s<u(*)<0.47 m/s.

Journal Article↗
PubMed2002

Met protein expression level correlates with survival in patients with late-stage nasopharyngeal carcinoma.

Met tyrosine kinase, the receptor for HGF/SF, is important in various cellular functions, including proliferation, mitogenesis, formation of branching tubules, angiogenesis, and tumor cell invasion and metastasis. However, the role of Met/HGF signaling pathway in nasopharyngeal carcinoma (NPC) has not been evaluated. In this study, we determined the expression profile and clinical correlation of Met/HGF in 66 cases of advanced NPC and the activation mechanisms of Met receptor in five NPC cell lines. Immunofluorescent staining and quantitative image analysis showed that the Met protein was expressed throughout the tumors and normal nasopharyngeal epithelia. Compared with NPC, the Met expression level was higher in columnar nasopharyngeal epithelium but lower in squamous nasopharyngeal epithelium. The normal interstitial stromal tissue expressed the lowest level of Met protein. HGF was detected mainly in the normal interstitial tissue surrounding the tumor. Met protein expression level was inversely correlated with patients' survival time; the correlation coefficient was -0.319 (P = 0.009). The mean survival time was 118 months in low Met expression group versus 52 months in high expression group (P = 0.0004). The cumulative 5-year survival rate was 77.68% in low expression group versus 38.24% in high expression group. The clinical stage was also significantly more advanced in high Met expression group. In the multivariate analysis, both clinical stage and Met protein expression level were independent prognostic indicators for patient survival. All of the five NPC cell lines tested did not express hgf mRNA but expressed met mRNA, and tyrosine phosphorylation of Met protein was mainly induced by exogenous HGF stimulation in these cells. No mutation was found in the tyrosine kinase and the juxtamembrane domains of Met receptor in the five NPC cell lines tested. These results indicate that: (a) high Met protein expression level correlates with poorer survival in late-stage NPC and serves as an independent prognostic indicator; and (b) the Met receptor in NPC is activated by its paracrine ligand HGF from the interstitial tissues rather than by an autocrine loop or its activating mutation.

Adult↗
PubMed2002

Identification of three cAMP-dependent protein kinase (PKA) phosphorylation sites within the major intracellular domain of neuronal nicotinic receptor alpha4 subunits.

This study determined whether all protein kinase A (PKA) and protein kinase C (PKC) phosphorylation sites on the alpha4 subunit of rat alpha4beta2 neuronal nicotinic receptors could be localized to the M3/M4 cytoplasmic domain of the protein, and investigated specific amino acid substrates for the kinases through two-dimensional phosphopeptide mapping and site-directed mutagenesis. Experiments were conducted using alpha4beta2 receptors expressed in Xenopus oocytes and a fusion protein corresponding to the M3/M4 cytoplasmic domain of alpha4 (alpha4(333-594) ). When oocytes expressing alpha4beta2 receptors were incubated with [(32) P]orthophosphate in order to label endogenous ATP stores, phosphorylation of alpha4 subunits was evident. Incubation of either immunoprecipitated receptors or the fusion protein with [(32) P]ATP and either PKA or PKC followed by trypsinization of the samples demonstrated that the kinases phosphorylated alpha4 subunits on multiple phosphopeptides, and that the phosphorylated full-length alpha4 protein and fusion protein produced identical phosphopeptide maps. Site-directed mutagenesis of Ser365, Ser472 and Ser491 to alanines in the fusion protein eliminated phosphopeptides phosphorylated by PKA, but not by PKC. Other mutations investigated, Ser470, Ser493, Ser517 and Ser590, did not alter the phosphopeptide maps. Results indicate that Ser365, Ser472 and Ser491 on neuronal nicotinic receptor alpha4 subunits are phosphorylated by PKA and are likely to represent post-translational regulatory sites on the receptor.

Animals↗
PubMed2002

Identifying cancer-related genes in nasopharyngeal carcinoma cell lines using DNA and mRNA expression profiling analyses.

The goals of this study were to evaluate the potential of detecting cryptic amplification and deletion of cancer-related genes using array-based comparative genomic hybridization (CGH), and to identify candidate cancer genes by combined parallel analyses of copy number and gene expression profiles in nasopharyngeal carcinoma (NPC) cell lines. We established global DNA copy number and mRNA expression profiles on human NPC cell lines using a high-density cDNA microarray. The DNA copy number alterations detected by array CGH were compared to the DNA copy number variations identified by metaphase CGH. A cryptic amplification at 3q26 was detected by array CGH, which was not found by metaphase CGH. By amplicon mapping and parallel analyses of DNA copy number and mRNA expression levels, we identified several candidates which could be important mediators in tumor formation or progression. Taken together, the combination of copy number and gene expression profiling using cDNA microarrays provides an improved strategy for gene discovery in human cancer.

Biomarkers, Tumor↗