bluuebunny/crossref_metadata_2025_split huggingface dataset:
Histatin 5-Derived Peptide with Improved Fungicidal Properties Enhances Human Immunodeficiency Virus Type 1 Replication by Promoting Viral Entry
Authors: Groot Fedde , Sanders Rogier W. , ter Brake Olivier , Nazmi Kamran , Veerman Enno C. I. , Bolscher Jan G. M. , Berkhout Ben 
Published: August 2006

ABSTRACT

Antimicrobial peptides are found in a number of body compartments and are secreted at mucosal surfaces, where they form part of the innate immune system. Many of these small peptides have a broad spectrum of inhibitory activity against bacteria, fungi, parasites, and viruses. Generally, the peptide's mode of action is binding and disruption of membranes due to its amphipathic properties. Histatin 5 is a salivary peptide that inhibits
Candida albicans
, an opportunistic fungus that causes oropharyngeal candidiasis in a majority of human immunodeficiency virus type 1 (HIV-1)-infected patients progressing towards AIDS. Previously, we increased the fungicidal properties of histatin 5 by replacing amino acids in the active domain of histatin 5 (Dh-5) (A. L. Ruissen, J. Groenink, E. J. Helmerhorst, E. Walgreen-Weterings, W. van’t Hof, E. C. Veerman, and A. V. Nieuw Amerongen, Biochem. J.
356:
361-368, 2001). In the current study, we tested the anti-HIV-1 activity of Dh-5 and its derivatives. Although Dh-5 inhibited HIV-1 replication, none of the peptide variants were more effective in this respect. In contrast, one of the derivatives, Dhvar2, significantly increased HIV-1 replication by promoting the envelope-mediated cell entry process. Most likely, Dhvar2 affects membranes, thereby facilitating fusion of viral and cellular membranes. This study shows that modification of antimicrobial peptides in order to improve their activity against a pathogen may have unpredictable and unwanted side effects on other pathogens.
Population Level Analysis of Human Immunodeficiency Virus Type 1 Hypermutation and Its Relationship with APOBEC3G and
vif
Genetic Variation
Authors: Pace Craig , Keller Jean , Nolan David , James Ian , Gaudieri Silvana , Moore Corey , Mallal Simon 
Published: August 2006

ABSTRACT

APOBEC3G and APOBEC3F restrict human immunodeficiency virus type 1 (HIV-1) replication in vitro through the induction of G→A hypermutation; however, the relevance of this host antiviral strategy to clinical HIV-1 is currently not known. Here, we describe a population level analysis of HIV-1 hypermutation in near-full-length clade B proviral DNA sequences (
n
= 127). G→A hypermutation conforming to expected APOBEC3G polynucleotide sequence preferences was inferred in 9.4% (
n
= 12) of the HIV-1 sequences, with a further 2.4% (
n
= 3) conforming to APOBEC3F, and was independently associated with reduced pretreatment viremia (reduction of 0.7 log
10
copies/ml;
P
= 0.001). Defective
vif
was strongly associated with HIV-1 hypermutation, with additional evidence for a contribution of
vif
amino acid polymorphism at residues important for APOBEC3G-
vif
interactions. A concurrent analysis of APOBEC3G polymorphism revealed this gene to be highly conserved at the amino acid level, although an intronic allele (6,892 C) was marginally associated with HIV-1 hypermutation. These data indicate that APOBEC3G-induced HIV-1 hypermutation represents a potent host antiviral factor in vivo and that the APOBEC3G-
vif
interaction may represent a valuable therapeutic target.
Cross-Interaction between JC Virus Agnoprotein and Human Immunodeficiency Virus Type 1 (HIV-1) Tat Modulates Transcription of the HIV-1 Long Terminal Repeat in Glial Cells
Authors: Kaniowska Dorota , Kaminski Rafal , Amini Shohreh , Radhakrishnan Sujatha , Rappaport Jay , Johnson Edward , Khalili Kamel , Del Valle Luis , Darbinyan Armine 
Published: August 2006

ABSTRACTThe human polyomavirus JC virus (JCV) is the causative agent of the fatal demyelinating disease progressive multifocal leukoencephalopathy (PML), which is commonly seen in AIDS patients. The bicistronic viral RNA, which is transcribed at the late phase of infection, is responsible for expressing the viral capsid proteins and a small regulatory protein, agnoprotein. Immunohistochemical analysis of brain tissue from subjects with AIDS/PML revealed colocalization of the human immunodeficiency virus type 1 (HIV-1) transactivator, Tat, and JCV agnoprotein in nucleus and cytoplasm of “bizarre” astrocytes. In accord with this observation, we detected the copresence of agnoprotein and Tat in human astrocytes upon infection with JCV and HIV-1 or in astrocytic cells expressing these proteins after transfection. Interestingly, results from infection of human astrocytes with HIV-1 and JCV showed a decrease in the level of HIV-1 replication in cells that are coinfected with JCV. Conversely, a slight increase in the level of JCV replication was observed in the presence of HIV-1. The copresence of JCV and HIV-1 in astrocytes prompted us to investigate the possible cross-interaction of agnoprotein with Tat and its impact on HIV-1 gene transcription. Our results demonstrate that agnoprotein through its N-terminal domain associates with Tat and the interaction causes the suppression of Tat-mediated enhancement of HIV-1 promoter activity in these cells. Results from RNA and protein binding assays showed that agnoprotein can inhibit the association of Tat with its target RNA sequence, TAR, and with cyclin T1. Furthermore, agnoprotein is able to interfere with cross-interaction of Tat with the p65 subunit of NF-κB and Sp1, whose functions are critical for Tat activation of the long terminal repeat. These observations unravel a new pathway for the molecular interaction of these two viruses in biologically relevant cells in the brains of AIDS/PML patients.
Does stretching increase ankle dorsiflexion range of motion? A systematic review
Authors: Radford J A , Burns J , Buchbinder R , Landorf K B , Cook C 
Published: August 2006

Background:Many lower limb disorders are related to calf muscle tightness and reduced dorsiflexion of the ankle. To treat such disorders, stretches of the calf muscles are commonly prescribed to increase available dorsiflexion of the ankle joint.Hypothesis:To determine the effect of static calf muscle stretching on ankle joint dorsiflexion range of motion.Study design:A systematic review with meta-analyses.Methods:A systematic review of randomised trials examining static calf muscle stretches compared with no stretching. Trials were identified by searching Cinahl, Embase, Medline, SportDiscus, and Central and by recursive checking of bibliographies. Data were extracted from trial publications, and meta-analyses performed that calculated a weighted mean difference (WMD) for the continuous outcome of ankle dorsiflexion. Sensitivity analyses excluded poorer quality trials. Statistical heterogeneity was assessed using the quantityI2.Results:Five trials met inclusion criteria and reported sufficient data on ankle dorsiflexion to be included in the meta-analyses. The meta-analyses showed that calf muscle stretching increases ankle dorsiflexion after stretching for ⩽15 minutes (WMD 2.07°; 95% confidence interval 0.86 to 3.27), >15–30 minutes (WMD 3.03°; 95% confidence interval 0.31 to 5.75), and >30 minutes (WMD 2.49°; 95% confidence interval 0.16 to 4.82). There was a very low to moderate statistical heterogeneity between trials. The meta-analysis results for ⩽15 minutes and >15–30 minutes of stretching were considered robust when compared with sensitivity analyses that excluded lower quality trials.Conclusions:Calf muscle stretching provides a small and statistically significant increase in ankle dorsiflexion. However, it is unclear whether the change is clinically important.
A retroviral expression system based on tetracycline-regulated tricistronic transactivator/repressor vectors for functional analyses of antiproliferative and toxic genes
Authors: Ausserlechner Michael J. , Obexer Petra , Deutschmann Andrea , Geiger Kathrin , Kofler Reinhard 
Published: August 2006

Abstract
Establishment of stably transfected mammalian cells with conditional expression of antiproliferative or proapoptotic proteins is often hampered by varying expression within bulk-selected cells and high background in the absence of the inducing drug. To overcome such limitations, we designed a gene expression system that transcribes the tetracycline-dependent rtTA2-M2-activator, TRSID-silencer, and selection marker as a tricistronic mRNA from a single retroviral vector. More than 92% of bulk-selected cells expressed enhanced green fluorescent protein or luciferase over more than three orders of magnitude in an almost linear, dose-dependent manner. To functionally test this system, we studied how dose-dependent expression of p27Kip1 affects proliferation and viability of SH-EP neuroblastoma cells. Low to moderate p27Kip1 expression caused transient G0-G1 accumulation without reduced viability, whereas high p27Kip1 levels induced significant apoptosis after 72 hours. This proves that this expression system allows concentration-dependent analysis of gene function and implicates p27Kip1 as a critical regulator of both proliferation and apoptosis in SH-EP neuroblastoma cells. [Mol Cancer Ther 2006;5(8):1927–34]
A mitochondrial targeted fusion peptide exhibits remarkable cytotoxicity
Authors: Law Benedict , Quinti Luisa , Choi Yongdoo , Weissleder Ralph , Tung Ching-Hsuan 
Published: August 2006

Abstract
A potent cytotoxic peptide (r7-kla) was synthesized by incorporating a mitochondrial membrane disrupting peptide, kla (klaklakklaklak), with a cell-penetrating domain, r7 (rrrrrrr). The IC50 of r7-kla (3.54 ± 0.11 μmol/L) was more than two orders of magnitude lower than that of kla. r7-kla induced cell death in both in vitro and in vivo environments, and showed rapid kinetics. Within minutes, the morphologic changes in cells and mitochondrial leakage were apparent by microscopy and was consistent with rapid apoptosis. Our results suggested that r7-kla is an apoptosis inducer and can be potentially used as an antitumor agent, especially when combined with the appropriate systemic delivery systems. [Mol Cancer Ther 2006;5(8):1944–9]
Inactivation of Akt by the epidermal growth factor receptor inhibitor erlotinib is mediated by HER-3 in pancreatic and colorectal tumor cell lines and contributes to erlotinib sensitivity
Authors: Buck Elizabeth , Eyzaguirre Alexandra , Haley John D. , Gibson Neil W. , Cagnoni Pablo , Iwata Kenneth K. 
Published: August 2006

Abstract
Signaling through the receptor for epidermal growth factor receptor (EGFR) is frequently deregulated in solid tumors. Erlotinib (Tarceva, OSI-774, OSI Pharmaceuticals, Inc., Melville, NY) is a low molecular weight, orally bioavailable inhibitor of the EGFR that has been approved for both non–small cell lung cancer and pancreatic cancers. Previous studies have indicated that sensitivity to EGFR antagonists correlated with HER-3 signaling for non–small cell lung cancer. Herein, we have sought to understand the signaling pathways that mediate erlotinib sensitivity for pancreatic and colorectal cancers. In a panel of 12 pancreatic tumor cell lines, we find that EGFR is coexpressed with HER-3 in all cell lines sensitive to erlotinib but not in insensitive cell lines. Erlotinib can block HER-3 phosphorylation in these sensitive cell lines, suggesting that HER-3 is transactivated by EGFR. Knockdown of HER-3 in BxPC3, an erlotinib-sensitive pancreatic tumor cell line, results in inhibition of the phosphorylation for both Akt and S6 and is associated with a decrease in cell proliferation and reduced sensitivity to erlotinib. Therefore, EGFR transactivation of HER-3 mediates Akt signaling and can contribute to erlotinib sensitivity for pancreatic tumors. We extended our analysis to a panel of 13 colorectal tumor cell lines and find that, like pancreatic, HER-3 is coexpressed with EGFR in the most erlotinib-sensitive cell lines but not in erlotinib-insensitive cell lines. These studies suggest that HER-3 could be used as a biomarker to select patients who are most likely to respond to erlotinib therapy. [Mol Cancer Ther 2006;5(8):2051–9]
Preclinical evaluation of tumor microvascular response to a novel antiangiogenic/antitumor agent RO0281501 by dynamic contrast-enhanced MRI at 1.5 T
Authors: Muruganandham Manickam , Lupu Mihaela , Dyke Jonathan P. , Matei Cornelia , Linn Michael , Packman Kathryn , Kolinsky Kenneth , Higgins Brian , Koutcher Jason A. 
Published: August 2006

Abstract
Inhibition of tumor angiogenesis is a promising approach in cancer treatment. The purpose of this study was to evaluate the vascular response of human lung tumor xenografts in vivo to RO0281501, an inhibitor of tyrosine kinase receptors, including vascular endothelial growth factor receptor 2, fibroblast growth factor receptor, and platelet-derived growth factor receptor, using dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI). Human non–small cell lung carcinoma (H460a) xenografts grown s.c. in athymic nu/nu mice were treated p.o. with the antiangiogenic agent RO0281501. Treatment-induced changes in tumor volume, epiphyseal growth plate thickness, and microvessel density assessed by CD31 immunohistochemistry were analyzed. Tumor vascular permeability and perfusion were measured in tumors using DCE-MRI with gadopentetate dimeglumine on a 1.5 T clinical scanner to assess vascular function. Treatment with RO0281501 resulted in significant growth retardation of H460a tumors. RO0281501-treated tumors showed histologic evidence of growth plate thickening and relatively lower microvessel density compared with the controls. Regarding DCE-MRI variables, the initial slope of contrast uptake and Akep were significantly decreased on day 7 of treatment. RO0281501 is a novel antiangiogenic/antitumor agent, which is active in the H460a xenograft model. Its effects on tumor vasculature can be monitored and assessed by DCE-MRI on a 1.5 T human MR scanner with clinically available gadopentetate dimeglumine contrast, which will facilitate clinical trials with this or similar agents. [Mol Cancer Ther 2006;5(8):1950–7]
Antitumor immune response induced by i.t. injection of vector-activated dendritic cells and chemotherapy suppresses metastatic breast cancer
Authors: Akbulut Hakan , Tang Yucheng , Akbulut K. Gonca , Maynard Jonathan , Zhang Lixin , Deisseroth Albert 
Published: August 2006

Abstract
S.c. injection of the Ad-sig-tumor-associated antigen (TAA)/ecdCD40L vector vaccine has been shown to induce a CD8 immune response against TAA for up to 1 year. The first goal of this article is to test if the injection of autologous dendritic cells infected ex vivo with the Ad-sig-TAA/ecdCD40L can increase the immune response induced against TAA. The second goal is to test the effect of adding local chemotherapy in the form of i.t. injection of the AdCDIRESE1A vector-directed chemotherapy on the immune response induced by i.t. injection of adenoviral vector-activated dendritic cells. The results show that the i.t. injection of the AdCDIRESE1A chemotherapy sensitization vector, which encodes the cytosine deaminase chemotherapy sensitization transcription unit, to the i.t. injection of Ad-sig-ecdCD40L vector-infected dendritic cells increased the level of suppression of the growth of the CCL-51 breast cancer cells. The combination of i.t. injection of the AdCDIRESE1A chemotherapy sensitization vector and Ad-sig-ecdCD40L vector-infected dendritic cells into s.c. CCL-51 breast cancer nodules suppressed the growth of uninjected metastatic tumor nodules in the lung. Finally, adding the i.t. injection of the AdCDIRESE1A chemotherapy sensitization vector to the i.t. administration of dendritic cells infected with a rat HER-2/neu (rH2N)–expressing vector (Ad-sig-rH2N/ecdCD40L) led to the induction of rH2N-specific antitumoral immunity in rH2N transgenic mice (which are anergic to the rH2N antigen). This anti-rH2N immune response suppressed the growth of established H2N-positive NT2 breast cancer more efficiently than did the vector-targeted chemotherapy or Ad-sig-rH2N/ecdCD40L-infected dendritic cell vaccine alone. [Mol Cancer Ther 2006;5(8):1975–85]
Expression profiling of ATP-binding cassette transporters in childhood T-cell acute lymphoblastic leukemia
Authors: Efferth Thomas , Gillet Jean-Pierre , Sauerbrey Axel , Zintl Felix , Bertholet Vincent , de Longueville Françoise , Remacle Jose , Steinbach Daniel 
Published: August 2006

Abstract
A major issue in the treatment of T-cell acute lymphoblastic leukemia (T-ALL) is resistance to chemotherapeutic drugs. Multidrug resistance can be caused by ATP-binding cassette (ABC) transporters. The majority of these proteins have not yet been examined in T-ALL. Using a newly developed microarray for the simultaneous quantification of 38 ABC transporter genes, we observed a consistent overexpression of ABCA2/ABCA3 in clinical samples of ALL. Therefore, we analyzed the association of these two genes with drug resistance. Treatment of CCRF-CEM and Jurkat cells with methotrexate, vinblastine, or doxorubicin led to an induction of ABCA3 expression, whereas a significant increase of ABCA2 expression was only observed in Jurkat cells. To study the causal relationship of ABCA2/A3 overexpression with drug resistance, we applied RNA interference (RNAi) technology. RNAi specific for ABCA2 or ABCA3 led to a partial decrease of expression in these two ABC transporters. Upon cotreatment of RNAi for ABCA2 with methotrexate and vinblastine, a partial decrease of ABCA2 expression as well as a simultaneous increase of ABCA3 expression was observed. Vice versa, ABCA3 RNAi plus drugs decreased ABCA3 and increased ABCA2 expression. This indicates that down-regulation of one ABC transporter was compensated by the up-regulation of the other. Application of RNAi for both ABCA2 and ABCA3 resulted in a more efficient reduction of the expression of both transporters. As a consequence, a significant sensitization of cells to cytostatic drugs was achieved. In conclusion, ABCA2 and ABCA3 are expressed in many T-ALL and contribute to drug resistance. [Mol Cancer Ther 2006;5(8):1986–94]
Carboplatin nanocapsules: a highly cytotoxic, phospholipid-based formulation of carboplatin
Authors: Hamelers Irene H.L. , van Loenen Esther , Staffhorst Rutger W.H.M. , de Kruijff Ben , de Kroon Anton I.P.M. 
Published: August 2006

Abstract
Platinum-based drugs are widely used in cancer chemotherapy. However, their clinical use is limited by systemic toxicity, rapid blood clearance, and the occurrence of resistance. Our research is aimed at increasing the therapeutic index of these drugs by encapsulation in a lipid formulation. Previously, we developed a method for efficient encapsulation of cisplatin in a lipid formulation, yielding cisplatin nanocapsules. Here, we show that carboplatin, a cisplatin-derived anticancer drug with different chemical properties, can be efficiently encapsulated in a lipid formulation by a similar method. The carboplatin nanocapsules exhibit a very high cytotoxicity in vitro: the IC50 value of carboplatin nanocapsules is up to a 1,000-fold lower than that of conventional carboplatin when tested on a panel of carcinoma cell lines. Cellular platinum content analysis and confocal fluorescent imaging of the interaction of the carboplatin nanocapsules with IGROV-1 cells indicate that the improved cytotoxicity is due to increased platinum accumulation in the cells, resulting from uptake of the formulation by endocytosis. [Mol Cancer Ther 2006;5(8):2007–12]
Resveratrol-induced cyclooxygenase-2 facilitates p53-dependent apoptosis in human breast cancer cells
Authors: Tang Heng-Yuan , Shih Ai , Cao H. James , Davis Faith B. , Davis Paul J. , Lin Hung-Yun 
Published: August 2006

AbstractCyclooxygenase-2 (COX-2) is antiapoptotic and is implicated in tumorigenesis. Recent reports, however, have also ascribed a proapoptotic action to inducible COX-2. We show here for the first time that a stilbene, resveratrol, induces nuclear accumulation of COX-2 protein in human breast cancer MCF-7 and MDA-MB-231 cell cultures. The induction of COX-2 accumulation by resveratrol is mitogen-activated protein kinase (MAPK; extracellular signal–regulated kinase 1/2)- and activator protein 1- dependent. Nuclear COX-2 in resveratrol-treated cells colocalizes with Ser15-phosphorylated p53 and with p300, a coactivator for p53-dependent gene expression. The interaction of COX-2, p53, and p300, as well as resveratrol-induced apoptosis, was inhibited by a MAPK activation inhibitor, PD98059. A specific inhibitor of COX-2, NS398, and small interfering RNA knockdown of COX-2 were associated with reduced p53 phosphorylation and consequent decrease in p53-dependent apoptosis in resveratrol-treated cells. We conclude that nuclear accumulation of COX-2 can be induced by resveratrol and that the COX has a novel intranuclear colocalization with Ser15-phosphorylated p53 and p300, which facilitates apoptosis in resveratrol-treated breast cancer cells. [Mol Cancer Ther 2006;5(8):2034–42]
Variability of the Horizontal Velocity Structure in the Upper 1600 m of the Water Column on the Equator at 10°W
Authors: Bunge Lucia , Provost Christine , Lilly Jonathan M. , D’Orgeville Marc , Kartavtseff Annie , Melice Jean-Luc 
Published: August 2006

Abstract
This paper presents initial results from new velocity observations in the eastern part of the equatorial Atlantic Ocean from a moored current-meter array. During the “EQUALANT” program (1999–2000), a mooring array was deployed around the equator near 10°W that recorded one year of measurements at various depths. Horizontal velocities were obtained in the upper 60 m from an upward-looking acoustic Doppler current profiler (ADCP) and at 13 deeper levels from current meters between 745 and 1525 m. To analyze the quasiperiodic variability observed in these records, a wavelet-based technique was used. Quasiperiodic oscillations having periods between 5 and 100 days were separated into four bands: 5–10, 10–20, 20–40, and 40–100 days. The variability shows (i) a strong seasonality (the first half of the series is dominated by larger periods than the second one) and (ii) a strong dependence with depth (some oscillations are present in the entire water column while others are only present at certain depths). For the oscillations that are present in the entire water column the origin of the forcing can be traced to the surface, while for the others the question of their origin remains open. Phase shifts at different depths generate vertical shears in the horizontal velocity component with relatively short vertical scales. This is especially visible in long-duration events (&gt;100 days) of the zonal velocity component. Comparison with a simultaneous lowered acoustic Doppler current profiler (LADCP) section suggests that some of these flows may be identified with equatorial deep jets. A striking feature is a strong vertical shear lasting about 7 months between 745 and 1000 m. These deep current-meter observations would then imply a few months of duration for the jets in this region.