Biomedical subjects
Publications and source records attributed to A Chen.
We report on a search for new resonant states in the process gamma gamma --> DD. A candidate C-even charmonium state is observed in the vicinity of 3.93 GeV/c2. The production rate and the angular distribution in the gamma gamma center-of-mass frame suggest that this state is the previously unobserved chi(c2)', the 2(3)P2 charmonium state.
High expression of epidermal growth factor receptor (EGFR) is found in a variety of solid tumors, including colorectal cancer. EGFR has been identified as a rational target for anticancer therapy. Curcumin, the yellow pigment of turmeric in curry, has received attention as a promising dietary supplement for cancer prevention and treatment. We recently reported that curcumin inhibited the growth of human colon cancer-derived Moser cells by suppressing gene expression of cyclinD1 and EGFR. The aim of the present study was to explore the molecular mechanisms underlying curcumin inhibition of gene expression of EGFR in colon cancer cells. The generality of the inhibitory effect of curcumin on gene expression of EGFR was verified in other human colon cancer-derived cell lines, including Caco-2 and HT-29 cells. Promoter deletion assays and site-directed mutageneses identified a binding site for the transcription factor early growth response-1 (Egr-1) in egfr promoter as a putative curcumin response element in regulating the promoter activity of the gene in Moser cells. Electrophoretic mobility shift assays demonstrated that curcumin significantly reduced the DNA-binding activity of the transcription factor Egr-1 to the curcumin response element. In addition, curcumin reduced the trans-activation activity of Egr-1 by suppressing egr-1 gene expression, which required interruption of the ERK signal pathway and reduction of the level of phosphorylation of Elk-1 and its activity. Taken together, our results demonstrated that curcumin inhibited human colon cancer cell growth by suppressing gene expression of EGFR through reducing the trans-activation activity of Egr-1. These results provided novel insights into the mechanisms of curcumin inhibition of colon cancer cell growth and potential therapeutic strategies for treatment of colon cancer.
BACKGROUND: Bismuth salts are not available worldwide. It remains unknown whether clarithromycin can replace bismuth salts as an adjuvant agent in the rescue regimens for Helicobacter pylori infection. We therefore designed the prospective study to compare the efficacies of two rescue therapies for H. pylori infection after standard triple therapies. PATIENTS AND METHODS: Ninety-three patients who failed H. pylori eradication using proton pump inhibitor plus clarithromycin and amoxicillin were randomly assigned to undergo rescue therapy with esomeprazole, clarithromycin, tetracycline and metronidazole (ECTM group, n = 46) or esomeprazole, bismuth subcitrate, tetracycline and metronidazole (EBTM group, n = 47). Follow-up endoscopy was performed at 8 weeks after the end of treatment to assess the treatment response. RESULTS: Intention-to-treat analysis demonstrated both groups had similar eradication rates (ECTM 74% vs. EBTM 77%; P = 0.76) and drug compliance (ECTM 94% vs. EBTM 96%; P = 0.68). However, the frequency of adverse events in the ECTM group was higher than that in EBTM group (ECTM 57% vs. EBTM 36%, P = 0.05). In the EBTM group, eradication rate of metronidazole-resistant strains was lower than that of metronidazole-susceptible strains (67%[8/12] vs. 100%[9/9], P = 0.05). However, eradication rates were similar between metronidazole-susceptible and metronidazole-resistant strains in ECTM group (69%[9/13] vs. 70%[7/10], P = 1.00). CONCLUSIONS: The new ECTM second-line therapy can achieve similar eradication rate as standard EBTM therapy. It may be very useful in countries where bismuth salts are not available.
AIMS: To examine the expression of extracellular matrix metalloprotease inducer (EMMPRIN) and matriptase in hepatocellular carcinoma (HCC) and to correlate this with tumour progression. METHODS AND RESULTS: Immunohistochemical analysis of EMMPRIN and matriptase was performed on tissue microarrays of 122 cases of HCC with various histological grades and/or clinical parameters. The expression of EMMPRIN and matriptase was undetectable in normal liver parenchyma of all eight control cases. However, among the 122 HCC cases, EMMPRIN and matriptase immunoreactivity was seen on the cell membrane and in the cytoplasm. The average immunostaining scores of EMMPRIN were 88 for grade I HCC, 195 for grade II HCC and 293 for grade III HCC. Of 85 HCC cases in 122 with detailed clinical TNM stages, the average immunostaining scores of EMMPRIN were 75 for stage T1, 177 for stage T2, 260 for stage T3 and 313 for stage T4 cases of HCC. In addition, the average immunostaining scores of matriptase were 84 for grade I HCC, 187 for grade II HCC, 302 for grade III HCC, and 72 for stage T1, 181 for stage T2, 224 for stage T3 and 284 for stage T4 cases of HCC. More advanced M and N stages of HCC were associated with higher intensity, greater percentages of tumour staining and immunostaining scores of EMMPRIN and matriptase. Higher EMMPRIN and matriptase immunostaining scores in HCCs also correlated significantly with tumour grading and TNM stages. CONCLUSIONS: Our findings demonstrate for the first time that EMMPRIN and matriptase are overexpressed in HCC. These may be novel biomarkers for the diagnosis and treatment of HCC.
CC chemokine receptor 7 (CCR7) is involved in the initiation of immune responses by mediating the migration of naïve T cells and mature dendritic cells to T-cell-rich zones of secondary lymphoid organs where antigen presentation occurs. To address whether CCR7 plays a role in the development of autoimmunity, we induced experimental autoimmune encephalomyelitis in CCR7-deficient mice on a C57BL/6 background (CCR7(-/-)) using the neuroantigen, myelin oligodendrocyte glycoprotein 35-55 amino acid peptide (MOG((35-55))) and Bordetella pertussis toxin (PTX). CCR7(-/-) mice acquired disease with an intensity similar to wild-type littermates. MOG((35-55))-specific lymphocyte responses were dominant in the spleen of CCR7(-/-) mice, rather than in lymph nodes as observed in wild-type mice. These results indicate that effective immune responses (with altered kinetics) can develop in the absence of CCR7 but develop in the spleen rather than lymph nodes as CCR7 is necessary for T and dendritic cells to enter lymph nodes.
Extracellular matrix metalloproteinase inducer (EMMPRIN) and the type II transmembrane serine protease, matriptase, are expressed in several human cancers and play an important role in tumor progression. The aim of the present study was to investigate the immuno-staining patterns of EMMPRIN and matriptase in patients with esophageal squamous cell carcinomas (SCC) and correlate the percentage tumor staining with tumor differentiation and clinical parameters. EMMPRIN and matriptase immunoreactivity was seen on the cell membrane and in the cytoplasm of tumor cells in all 41 cases of esophageal SCC evaluated. The percentage tumor staining of EMMPRIN was 48 +/- 3% for well differentiated, 73 +/- 3% for moderately differentiated, and 92 +/- 3% for poorly differentiated esophageal SCC. Higher percentage tumor staining with EMMPRIN correlated significantly with poorly differentiated esophageal SCC (P < 0.05). The percentage tumor staining with matriptase correlated significantly with tumor differentiation (52 +/- 3% for well differentiated, 85 +/- 2% for moderately differentiated, and 88 +/- 3% for poorly differentiated esophageal SCC). Additionally, higher percentage tumor staining with matriptase was significantly correlated with the advanced N and M stages (P < 0.05). Our results demonstrate that EMMPRIN and matriptase are over-expressed in esophageal SCC and are correlated with advanced clinicopathological stages. Pharmacological agents targeting EMMPRIN and matriptase expressions may be beneficial in the treatment of esophageal SCC.
BACKGROUND AND PURPOSE: Perfusion CT (PCT) has the ability to measure quantitative values and produce maps of cerebral blood flow (CBF), cerebral blood volume (CBV), and mean transit time (MTT). We assessed cerebral hemodynamics by using these parameters and acetazolamide challenge in patients with cerebrovascular steno-occlusive disease. METHODS: Fifteen patients underwent PCT with acetazolamide challenge. Comparison of mean CBF, CBV, and MTT was determined between hemispheres and before and after acetazolamide challenge. Hemispheric ratio and percent change due to acetazolamide administration were also calculated. Absolute values and percent changes 2 SDs outside the mean from the nonstenotic hemispheres were defined as abnormal. RESULTS: Significant decreases in CBF (-25.1%, P = .003) and significant increases in MTT (47.1%, P < .001) were found in stenotic hemispheres. After acetazolamide challenge, significant changes in CBF (-39.5%, P < .001) and MTT (92.9%, P < .001) were also seen. The acetazolamide test significantly decreased CBF hemispheric ratio (-20.3%, P < .001) and increased MTT hemispheric ratio (30.8%, P = .002), making both maps more asymmetric. Significance in CBF and MTT percent changes (P < .001 and P = .005, respectively) was found between hemispheres. When CBF percent changes were assumed to represent the true determinant of hemodynamic impairment, normal ranges of baseline MTT value and MTT percent changes demonstrated sensitivities of 66.7% and 100% and specificities of 58.3% and 75%, respectively, for detecting patients with hemodynamic impairment. CONCLUSION: Parameters obtained from PCT with acetazolamide are promising for the evaluation of cerebral hemodynamics in patients with cerebrovascular steno-occlusive disease.
The liquid-gas system is expected to exhibit distinct dynamic behavior in the fluid's critical region (model H). We present molecular dynamics simulations of a Lennard-Jones fluid model starting from specially designed, near-equilibrium, initial conditions. By following the fluid's relaxation towards equilibrium, we calculate the requisite transport coefficients in the critical region. The results yield the scaling behavior of the thermal diffusion coefficient D(T) approximately xi(-1.023+/-0.018) (xi is the correlation length) and a nonconventional divergent heat conductivity, all of which are in accord with mode-coupling and renormalization group predictions, as well as some experimental data.
We present a measurement of the Cabibbo-Kobayashi-Maskawa matrix element /Vub/, based on 253 fb(-1) of data collected by the Belle detector at the KEKB e+ e- asymmetric collider. Events are tagged by fully reconstructing one of the B mesons, produced in pairs from Gamma(4S). The signal for b --> u semileptonic decay is distinguished from the b --> c background using the hadronic mass Mx, the leptonic invariant mass squared q2 and the variable P+ [triple bond] Ex - /px/. The results are obtained for events with p(l)* > or = 1 GeV/c, in three kinematic regions (1) Mx < 1.7 GeV/c2, (2) Mx < 1.7 GeV/c2 combined with q2 > 8 GeV2/c2, and by (3) P+ < 0.66 GeV/c. The matrix element /Vub/ is found to be (4.09 +/- 0.19 +/- 0.20(+0.14) -0.15 +/- 0.18) x 10(-3), where the errors are statistical, systematic including Monte Carlo modeling, theoretical, and from shape function parameter determination, respectively.
We report measurements of B meson decays to two kaons using 253 fb(-1) of data collected with the Belle detector at the KEKB energy-asymmetric e+ e- collider. We find evidence for signals in B+ --> K0 K+ and B0 --> K0 K0 with significances of 3.0sigma and 3.5sigma, respectively. (Charge-conjugate modes are included.) The corresponding branching fractions are measured to be [symbol: see text](B+ --> K0 K+) = (1.0 +/- 0.4 +/- 0.1) x 10(-6) and [symbol: see text](B0 --> K0 K0) = (0.8 +/- 0.3 +/- 0.1) x 10(-6). These decay modes are examples of hadronic bd transitions. No signal is observed in the decay B0 --> K+ K-, and we set an upper limit of 3.7 x 10(-7) at 90% confidence level.
Using 281 fb-1 of data from the Belle experiment recorded at or near the (4S) resonance, we have measured the rates of the "wrong-sign" decays D0 --> K+ pi- pi0 and D0 --> K+ pi- pi+ pi- relative to those of the Cabibbo-favored decays D0 --> K- pi+ pi0 and D0 --> K- pi+ pi+ pi-. These wrong-sign decays proceed via a doubly Cabibbo-suppressed amplitude or via D0-D0 mixing; the latter has not yet been observed. We obtain R(WS)(K pi pi0) = [0.229 +/- 0.015(stat)(+0.013)(-0.009)(syst)]% and R(WS)(K3pi) = [0.320 +/- 0.018(stat)(+0.018)(0.013)(syst)]%. The CP asymmetries are measured to be -0.006 +/- 0.053 and -0.018 +/- 0.044 for the K+ pi- pi0 and K+ pi- pi+ pi- final states, respectively.
We present the results of a study of the charmless vector-vector decay B+ --> rho+ K*0, based on 253 fb(-1) of data collected with the Belle detector at the KEKB asymmetric-energy e+ e- collider. We obtain the branching fraction B(B+ --> rho+ K*0) = [8.9 +/- 1.7(stat) +/- 1.2(syst)] x 10(-6). We also perform a helicity analysis of the rho and K* vector mesons, and obtain the longitudinal polarization fraction f(L)(B+ --> rho+ K*0) = 0.43 +/- 0.11(stat)(-0.02)(+0.05) (syst).
We present a new measurement of the time-dependent CP-violating parameters in B(0)--> pi(+)pi(-) decays with 275 x 10(6) BB pairs collected with the Belle detector at the KEKB asymmetric-energy e(+)e(-) collider operating at the Gamma(4S) resonance. We find 666 +/- 43 B(0) --> pi(+)pi(-) events and measure the CP-violating parameters: S(pipi) = -0.67 +/- 0.16(stat) +/- 0.06(syst) and A(pipi) = +0.56 +/- 0.12(stat) +/- 0.06(syst). We find evidence for large direct CP violation with a significance greater than 4 standard deviations for any S(pipi) value. Using isospin relations, we obtain 95.4% confidence intervals for the Cabibbo-Kobayashi-Maskawa quark-mixing matrix angle phi(2) of 0 degree < phiv(2) < 19 degrees and 71 degrees < phi(2) < 180 degrees.
CP violation in B-->J/PsiK* decays is studied using an angular analysis in a data sample of 253 fb(-1) recorded with the Belle detector at the KEKB e(+)e(-) collider. The flavor separated measurements of the decay amplitudes indicate no evidence for direct CP violation. T-odd CP violation is studied using the asymmetries in triple product correlations, and the results are consistent with the standard model null predictions. The time-dependent angular analysis gives the following values of CP-violating parameters: sin(2phi(1) = 0.24 +/- 0.31 +/- 0.05 and cos(2phi(1)=0.56 +/- 0.79 +/- 0.11.
We report the first observation of the radiative hyperonic B decay B+ --> plambdagamma, using a 140 fb(-1) data sample recorded on upsilom(4S) resonance with the Belle detector at the KEKB asymmetric energy e+e- collider. The measured branching fraction is [symbol: see text](B+ --> plambdagamma) = (2.16(+0.58)(-0.53) +/- 0.20) x 10(-6). We examine its M(plambda) distribution and observe a peak near threshold. This feature is expected by the short-distance b --> sgamma transition. A search for B+ --> pepsilon0gamma yields no significant signal, and we set a 90% confidence-level upper limit on the branching fraction of [symbol: see textB+ --> pepsilon0gamma <4.6 x 10(-6).
We present a measurement of CP-violation parameters in the B0 --> K(s)0K(s)0K(s)0 decay based on a sample of 275 x 10(6) BB pairs collected at the upsilon(4S) resonance with the Belle detector at the KEKB energy-asymmetric e+e- collider. One neutral B meson is fully reconstructed in the decay B0 --> K(s)0K(s)0K(s)0, and the flavor of the accompanying B meson is identified from its decay products. CP-violation parameters are obtained from the asymmetry in the distributions of the proper-time interval between the two B decays: S = +1.26 +/- 0.68(stat) +/- 0.20(syst) and [symbol: see text] = +0.54 +/- 0.34(stat) +/- 0.09(syst).
We report evidence for B(0) --> D(0)D(-) and the first observation of the decay modes B(-) --> D(0)D(-) and B(-) --> D(0)D(*-) based on a sample of 152 x 10(6) BB events collected by the Belle detector at KEKB. The branching fractions for B(0) --> D(+) D(-), B--->D(0)D(-), and B--> D(0)D(*-) are found to be (1.91 +/- 0.51 +/- 0.30) x10(-4), (4.83 +/- 0.78 +/- 0.58) x 10(-4), and (4.57 +/- 0.71 +/- 0.56) x 10(-4), respectively. Charge asymmetries in the B---> D(0)D(-) and B(-) --> D(0)D(*-) channels are consistent with zero.
We present a new measurement of CP-violation parameters in B(0)-->K(0)(S)pi(0)gamma decay based on a sample of 275 x 10(6) BB pairs collected at the Gamma(4S) resonance with the Belle detector at the KEKB energy-asymmetric e(+)e(-) collider. One of the B mesons is fully reconstructed in the B(0)-->K(0)(S)pi(0)gamma decay. The flavor of the accompanying B meson is identified from its decay products. CP-violation parameters are obtained from the asymmetry in the distribution of the proper time intervals between the two B decays. We obtain SK(0)(S)(pi(0)gamma) = -0.58(+0.46)(-0.38)(stat) +/- 0.11(syst) and AK(0)(S)(pi(0)gamma) = +0.03 +/- 0.34(stat) +/- 0.11(syst), for the K(0)(S)pi(0) invariant mass covering the full range up to 1.8 GeV/c2. We also measure the CP-violation parameters for the case B(0)-->K(*0)(-->K(0)(S)pi(0))gamma and obtain S(K(*0)gamma) = -0.79(+0.63)(-0.50)(stat) +/- 0.10(syst) for A(K(*0)gamma) fixed at 0.