Combination of oncolytic adenovirus and luteolin exerts synergistic antitumor effects in colorectal cancer cells and a mouse model

In recent years, oncolytic viruses have attracted increasing interest due to their potent antitumor effects. Luteolin, a natural product, has additionally been observed to exhibit various pharmacological antitumor activities. Previously, a novel dual-targeting oncolytic adenovirus, complement decay-accelerating factor (CD55)-tumor necrosis factor ligand superfamily member 10 (TRAIL), was constructed, which exhibited significant growth inhibitory effects in various types of tumor cell. The present study investigated whether the combination of luteolin and CD55-TRAIL was able to exert a synergistic antitumor effect in colorectal carcinoma (CRC) cells. The cytotoxicity and tumor cell apoptosis mediated by combination treatment in CRC cells were detected via an MTT assay, Hoechst staining and western blotting, respectively. Tumor growth in vivo was examined in a CRC mouse xenograft model following various treatments. The results demonstrated that the addition of luteolin enhanced oncolytic adenovirus-mediated enhanced green fluorescent protein, early region 1A and TRAIL expression. The combination of CD55-TRAIL with luteolin synergistically inhibited tumor growth and promoted CRC cellular apoptosis in vitro and in vivo. Additionally, the combination of CD55-TRAIL with luteoli n significa ntly decrea sed cy totoxicit y in lung/bronchial normal epithelial cells, compared with single treatment

Optical and transport properties in doped two-leg ladder antiferromagnet

Within the t-J model, the optical and transport properties of the doped two-leg ladder antiferromagnet are studied based on the fermion-spin theory. It is shown that the optical and transport properties of the doped two-leg ladder antiferromagnet are mainly governed by the holon scattering. The low energy peak in the optical conductivity is located at a finite energy, while the resistivity exhibits a crossover from the high temperature metallic-like behavior to the low temperature insulating-like behavior, which are consistent with the experiments.Comment: 13 pages, 5 figures, accepted for publication in Phys. Rev. B65 (2002) (April 15 issue

Schizophrenia is not associated with the ERBB3 gene in a Han Chinese population sample: Results from case-control and family-based studies

ERBB3 (v-erb-b2 erythroblastic leukemia viral oncogene homolog 3), encoding a receptor of neuregulin-1 (NRG1), has been considered a functional candidate gene for schizophrenia susceptibility. In order to investigate a relationship between ERBB3 gene and schizophrenia in the Chinese population, case-control and family-based studies were carried out in 470 cases matched by controls, and in 532 family trios. Our results failed to show any evidence of significant association between the ERBB3 rs2292238 polymorphism and schizophrenia

Q2Q^2 Dependence of Quadrupole Strength in the γ∗p→Δ+(1232)→pπ0\gamma^*p\to\Delta^+(1232)\to p \pi^0 Transition

Models of baryon structure predict a small quadrupole deformation of the nucleon due to residual tensor forces between quarks or distortions from the pion cloud. Sensitivity to quark versus pion degrees of freedom occurs through the $Q^2$ dependence of the magnetic ($M_{1+}$), electric ($E_{1+}$), and scalar ($S_{1+}$) multipoles in the $\gamma^* p \to \Delta^+ \to p \pi^0$ transition. We report new experimental values for the ratios $E_{1+}/M_{1+}$ and $S_{1+}/M_{1+}$ over the range $Q^2$= 0.4-1.8 GeV$^2$, extracted from precision $p(e,e 'p)\pi^{\circ}$ data using a truncated multipole expansion. Results are best described by recent unitary models in which the pion cloud plays a dominant role.Comment: 5 pages, 5 figures, 1 table. To be published in Phys. Rev. Lett. (References, figures and table updated, minor changes.

Quark-Hadron Duality in Spin Structure Functions g(1)(p) and g(1)(d)

New measurements of the spin structure functions of the proton and deuteron g(1)(p)(x,Q2) and g(1)(d)(x,Q2) in the nucleon resonance region are compared with extrapolations of target-mass-corrected next-to-leading-order (NLO) QCD fits to higher energy data. Averaged over the entire resonance region (W \u3c2 \u3eGeV), the data and QCD fits are in good agreement in both magnitude and Q2 dependence for Q2 \u3e1.7 GeV2/c2. This global duality appears to result from cancellations among the prominent local resonance regions: in particular strong σ3/2 contributions in the Δ (1232) region appear to be compensated by strong σ1/2 contributions in the resonance region centered on 1.5 GeV. These results are encouraging for the extension of NLO QCD fits to lower W and Q2 than have been used previously

The e p -> e' p eta reaction at and above the S11(1535) baryon resonance

New cross sections for the reaction e p -> ep eta are reported for total center of mass energy W = 1.5--1.86 GeV and invariant momentum transfer Q^2 = 0.25--1.5 GeV^2. This large kinematic range allows extraction of important new information about response functions, photocouplings, and eta N coupling strengths of baryon resonances. Expanded W coverage shows sharp structure at W \~ 1.7 GeV; this is shown to come from interference between S and P waves and can be interpreted in terms of known resonances. Improved values are derived for the photon coupling amplitude for the S11(1535) resonance.Comment: 11 pages, RevTeX, 5 figures, submitted to Phys. Rev. Let

Transcriptional Regulation of PP2A-Aα Is Mediated by Multiple Factors Including AP-2α, CREB, ETS-1, and SP-1

Protein phosphatases-2A (PP-2A) is a major serine/threonine phosphatase and accounts for more than 50% serine/threonine phosphatase activity in eukaryotes. The holoenzyme of PP-2A consists of the scaffold A subunit, the catalytic C subunit and the regulatory B subunit. The scaffold subunits, PP2A-Aα/β, provide a platform for both C and B subunits to bind, thus playing a crucial role in providing specific PP-2A activity. Mutation of the two genes encoding PP2A-Aα/β leads to carcinogenesis and likely other human diseases. Regulation of these genes by various factors, both extracellular and intracellular, remains largely unknown. In the present study, we have conducted functional dissection of the promoter of the mouse PP2A-Aα gene. Our results demonstrate that the proximal promoter of the mouse PP2A-Aα gene contains numerous cis-elements for the binding of CREB, ETS-1, AP-2α, SP-1 besides the putative TFIIB binding site (BRE) and the downstream promoter element (DPE). Gel mobility shifting assays revealed that CREB, ETS-1, AP-2α, and SP-1 all bind to PP2A-Aα gene promoter. In vitro mutagenesis and reporter gene activity assays reveal that while SP-1 displays negative regulation, CREB, ETS-1 and AP-2Aα all positively regulate the promoter of the PP2A-Aα gene. ChIP assays further confirm that all the above transcription factors participate the regulation of PP2A-Aα gene promoter. Together, our results reveal that multiple transcription factors regulate the PP2A-Aα gene

Measurement of Inclusive Spin Structure Functions of the Deuteron

We report the results of a new measurement of spin structure functions of the deuteron in the region of moderate momentum transfer ($Q^2$ = 0.27 -- 1.3 (GeV/c)$^2$) and final hadronic state mass in the nucleon resonance region ($W$ = 1.08 -- 2.0 GeV). We scattered a 2.5 GeV polarized continuous electron beam at Jefferson Lab off a dynamically polarized cryogenic solid state target ($^{15}$ND$_3$) and detected the scattered electrons with the CEBAF Large Acceptance Spectrometer (CLAS). From our data, we extract the longitudinal double spin asymmetry $A_{||}$ and the spin structure function $g_1^d$. Our data are generally in reasonable agreement with existing data from SLAC where they overlap, and they represent a substantial improvement in statistical precision. We compare our results with expectations for resonance asymmetries and extrapolated deep inelastic scaling results. Finally, we evaluate the first moment of the structure function $g_1^d$ and study its approach to both the deep inelastic limit at large $Q^2$ and to the Gerasimov-Drell-Hearn sum rule at the real photon limit ($Q^2 \to 0$). We find that the first moment varies rapidly in the $Q^2$ range of our experiment and crosses zero at $Q^2$ between 0.5 and 0.8 (GeV/c)$^2$, indicating the importance of the $\Delta$ resonance at these momentum transfers.Comment: 13 pages, 8 figures, ReVTeX 4, final version as accepted by Phys. Rev.

High Prevalence of Extended-Spectrum Beta Lactamases among Salmonella enterica Typhimurium Isolates from Pediatric Patients with Diarrhea in China

We investigated the extended-spectrum beta lactamases among 62 Salmonella enterica Typhimurium isolates recovered from children with diarrhea in a Chinese pediatric hospital. A large proportion of S. enterica Typhimurium isolates were resistant to multiple antimicrobial agents, including ampicillin (90.3%), tetracycline (80.6%), trimethoprim/sulfamethoxazole (74.2%), chloramphenicol (66.1%), cefotaxime (27.4%). Forty-nine (79.0%) of S. enterica Typhimurium isolates were positive for blaTEM-1b and resistant to ampicillin. Thirteen S. enterica Typhimurium isolates (21.0%) were positive for blaCTX-M-1-group and blaCTX-M-9-group, and all isolates harboring blaCTX-M genes were positive for ISEcp1. Two main clones (PFGE type A and D) accounted for nearly 70% of S. enterica Typhimurium isolates, and 7 CTX-M-producing isolates belonged to PFGE type D. Collectively, our data reveal multi-drug resistance and a high prevalence of extended spectrum beta lactamases among S. enterica Typhimurium isolates from children in China. In addition, we report the first identification of blaCTX-M-55 within Salmonella spp. Our data also suggest that clonal spread is responsible for the dissemination of S. enterica Typhimurium isolates

Recurrent DNMT3A R882 Mutations in Chinese Patients with Acute Myeloid Leukemia and Myelodysplastic Syndrome

Somatic mutations of DNMT3A gene have recently been reported in acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). We examined the entire coding sequences of DNMT3A gene by high-resolution melting analysis and sequencing in Chinese patients with myeloid malignancies. R882 mutations were found in 12/182 AML and in 4/51 MDS, but not in either 79 chronic myeloid leukemia (CML), or 57 myeloproliferative neoplasms (MPNs), or 4 chronic monomyelocytic leukemia. No other DNMT3A mutations were detected in all patients. R882 mutations were associated with old age and more frequently present in monoblastic leukemia (M4 and M5, 7/52) compared to other subtypes (5/130). Furthermore, 14/16 (86.6%) R882 mutations were observed in patients with normal karyotypes. The overall survival of mutated MDS patients was shorter than those without mutation (median 9 and 25 months, respectively). We conclude that DNMT3A R882 mutations are recurrent molecular aberrations in AML and MDS, and may be an adverse prognostic event in MDS