bluuebunny/crossref_metadata_2025_split huggingface dataset:
Quantifying the Activity of Adenoviral E1A CR2 Deletion Mutants Using Renilla Luciferase Bioluminescence and 3′-Deoxy-3′-[18F]Fluorothymidine Positron Emission Tomography Imaging
Authors: Leyton Julius , Lockley Michelle , Aerts Joeri L. , Baird Sarah K. , Aboagye Eric O. , Lemoine Nicholas R. , McNeish Iain A. 
Published: September 2006

Abstract
The adenoviral E1A CR2 mutant dl922-947 has potent activity in ovarian cancer. We have used Renilla luciferase bioluminescence imaging to monitor viral E1A expression and replication and [18F]fluorothymidine positron emission tomography ([18F]FLT-PET) to quantify the activity of dl922-947 in vivo. We created dlCR2 Ren, with the same E1A CR2 deletion as dl922-947 and the luciferase gene from Renilla reniformis downstream of E1. Light emitted from s.c. and i.p. IGROV1 ovarian carcinoma xenografts was measured following treatment with dlCR2 Ren. Mice bearing s.c. IGROV1 xenografts were injected with 2.96 to 3.7 MBq of [18F]FLT 48 and 168 hours following i.t. injection of dl922-947 or control virus Ad LM-X. The presence of Renilla luciferase in dlCR2 Ren did not reduce in vitro nor in vivo potency compared with dl922-947. Light emission correlated closely with E1A expression in vitro and peaked 48 hours after dlCR2 Ren injection in both s.c. and i.p. IGROV1 xenografts. It diminished by 168 hours in s.c. tumors but persisted for at least 2 weeks in i.p. models. Normalized tumor [18F]FLT uptake at 60 minutes (NUV60), fractional retention, and area under radioactivity curve all decreased marginally 48 hours after dl922-947 treatment and significantly at 168 hours compared with controls. There was a close linear correlation between NUV60 and both tumor proliferation (Ki67 labeling index) and thymidine kinase 1 expression. Renilla luciferase bioluminescence and [18F]FLT-PET imaging are capable of quantifying the activity and effectiveness of E1A CR2–deleted adenoviral mutants in ovarian cancer. (Cancer Res 2006; 66(18): 9178-85)
PDZ-Binding Kinase/T-LAK Cell-Originated Protein Kinase, a Putative Cancer/Testis Antigen with an Oncogenic Activity in Breast Cancer
Authors: Park Jae-Hyun , Lin Meng-Lay , Nishidate Toshihiko , Nakamura Yusuke , Katagiri Toyomasa 
Published: September 2006

Abstract
Breast cancer is one of the most common cancers among women. To discover molecular targets that are applicable for development of novel breast cancer therapy, we previously did genome-wide expression profile analysis of 81 breast cancers and found dozens of genes that were highly and commonly up-regulated in breast cancer cells. Among them, we here focused on one gene that encodes PDZ-binding kinase/T-LAK cell-originated protein kinase (PBK/TOPK), including a kinase domain. Northern blot analyses using mRNAs of normal human organs, breast cancer tissues, and cancer cell lines indicated this molecule to be a novel cancer/testis antigen. Reduction of PBK/TOPK expression by small interfering RNA resulted in significant suppression of cell growth probably due to dysfunction in the cytokinetic process. Immunocytochemical analysis with anti-PBK/TOPK antibody implicated a critical role of PBK/TOPK in an early step of mitosis. PBK/TOPK could phosphorylate histone H3 at Ser10 in vitro and in vivo, and mediated its growth-promoting effect through histone H3 modification. Because PBK/TOPK is the cancer/testis antigen and its kinase function is likely to be related to its oncogenic activity, we suggest PBK/TOPK to be a promising molecular target for breast cancer therapy. (Cancer Res 2006; 66(18): 9186-95)
All-trans-Retinoic Acid Improves Differentiation of Myeloid Cells and Immune Response in Cancer Patients
Authors: Mirza Noweeda , Fishman Mayer , Fricke Ingo , Dunn Mary , Neuger Anthony M. , Frost Timothy J. , Lush Richard M. , Antonia Scott , Gabrilovich Dmitry I. 
Published: September 2006

AbstractAbnormal dendritic cell differentiation and accumulation of immature myeloid suppressor cells (ImC) is one of the major mechanisms of tumor escape. We tested the possibility of pharmacologic regulation of myeloid cell differentiation using all-trans-retinoic acid (ATRA). Eighteen patients with metastatic renal cell carcinoma were treated with ATRA followed by s.c. interleukin 2 (IL-2). Eight healthy individuals comprised a control group. As expected, the cancer patients had substantially elevated levels of ImC. We observed that ATRA dramatically reduced the number of ImC. This effect was observed only in patients with high plasma concentration of ATRA (&gt;150 ng/mL), but not in patients with lower ATRA concentrations (&lt;135 ng/mL). Effects of ATRA on the proportions of different dendritic cell populations were minor. However, ATRA significantly improved myeloid/lymphoid dendritic cell ratio and the ability of patients' mononuclear cells to stimulate allogeneic T cells. This effect was associated with significant improvement of tetanus-toxoid–specific T-cell response. During the IL-2 treatment, the ATRA effect was completely eliminated. To assess the role of IL-2, specimens from 15 patients with metastatic renal cell carcinoma who had been treated with i.v. IL-2 alone were analyzed. In this group also, IL-2 significantly reduced the number and function of dendritic cells as well as T-cell function. These data indicate that ATRA at effective concentrations eliminated ImC, improved myeloid/lymphoid dendritic cell ratio, dendritic cell function, and antigen-specific T-cell response. ATRA treatment did not result in significant toxicity and it could be tested in therapeutic combination with cancer vaccines. (Cancer Res 2006; 66(18): 9299-307)
Role of Apoptotic Nuclease Caspase-Activated DNase in Etoposide-Induced Treatment-Related Acute Myelogenous Leukemia
Authors: Hars Eszter S. , Lyu Yi Lisa , Lin Chao-Po , Liu Leroy F. 
Published: September 2006

Abstract
Etoposide-induced treatment-related acute myelogenous leukemia (t-AML) is characterized by rearrangements of the mixed lineage leukemia (MLL) gene with one of its &gt;50 partner genes, most probably as a consequence of etoposide-induced DNA double-strand breaks (DSBs). Recent studies have shown that etoposide-induced DSBs occur predominantly within the breakpoint cluster region (bcr) of the MLL gene. However, bcr-specific DSBs induced by etoposide are not topoisomerase II–linked but the result of apoptotic nuclease–mediated DNA cleavage. Here, we test the involvement of caspase-activated DNase (CAD) and other apoptotic components in etoposide-induced gene rearrangements using two methods. First, we measured the effect of etoposide on the integration frequency of a transfected plasmid. Etoposide strongly stimulated plasmid integration in CAD cDNA–complemented mouse embryonic fibroblasts (MEFs) but not in CAD knockout (KO) MEFs. Consistently, down-regulation of ICAD (inhibitor of CAD, also required for proper folding of CAD) in an HT29-derived cell line, which leads to decreased CAD activity, significantly reduced etoposide-induced plasmid integration. Second, we used long-template inverse PCR to focus on gene rearrangements at the MLL locus. Etoposide stimulated MLL fusion product formation in CAD cDNA–complemented MEFs but not in CAD KO MEFs. Together, these results suggest that CAD and other apoptotic components may play an important role in etoposide-induced t-AML. (Cancer Res 2006; 66(18): 8975-9)
Magnetic Resonance Visualization of Tumor Angiogenesis by Targeting Neural Cell Adhesion Molecules with the Highly Sensitive Gadolinium-Loaded Apoferritin Probe
Authors: Geninatti Crich Simonetta , Bussolati Benedetta , Tei Lorenzo , Grange Cristina , Esposito Giovanna , Lanzardo Stefania , Camussi Giovanni , Aime Silvio 
Published: September 2006

Abstract
Tumor vessel imaging could be useful in identifying angiogenic blood vessels as well as being a potential predictive marker of antiangiogenic treatment response. We recently reported the expression of the neural cell adhesion molecule (NCAM) in the immature and tumor endothelial cell (TEC) lining vessels of human carcinomas. Exploiting an in vivo model of human tumor angiogenesis obtained by implantation of TEC in Matrigel in severe combined immunodeficiency mice, we aimed to image angiogenesis by detecting the expression of NCAM with magnetic resonance imaging. The imaging procedure consisted of (a) targeting NCAMs with a biotinylated derivative of C3d peptide that is known to have high affinity for these epitopes and (b) delivery of a streptavidin/gadolinium (Gd)-loaded apoferritin 1:1 adduct at the biotinylated target sites. The remarkable relaxation enhancement ability of the Gd-loaded apoferritin system allowed the visualization of TEC both in vitro and in vivo when organized in microvessels connected to the mouse vasculature. Gd-loaded apoferritin displayed good in vivo stability and tolerability. The procedure reported herein may be easily extended to the magnetic resonance visualization of other epitopes suitably targeted by proper biotinylated vectors. (Cancer Res 2006; 66(18): 9196-201)
Epigenetic Silencing of Occludin Promotes Tumorigenic and Metastatic Properties of Cancer Cells via Modulations of Unique Sets of Apoptosis-Associated Genes
Authors: Osanai Makoto , Murata Masaki , Nishikiori Nami , Chiba Hideki , Kojima Takashi , Sawada Norimasa 
Published: September 2006

Abstract
Occludin is the first identified integral protein for the tight junction (TJ), and its long COOH-terminal domain is considered to have functions in receiving and transmitting cell survival signals. Loss of TJ-associated molecules, such as occludin, has been correlated with tumor progression in carcinogenesis; however, the precise molecular mechanisms explaining its loss of expression and whether occludin expression has any effects on cancer phenotypes remain to be clarified. Here, we show that forced expression of occludin in cancer cells exhibits enhanced sensitivity to differently acting apoptogenic factors, and thus inhibits the tumorigenicity of transformed cells, via modulation of unique sets of apoptosis-associated genes. In addition, studies using deletion mutants of occludin constructs show that 44 amino acids at the COOH-terminal end play a critical role in modifying the cellular phenotypes. Interestingly, occludin decreases cellular invasiveness and motility, thereby abrogating metastatic potencies of cancer cells. We also found that occludin expression is silenced by CpG island hypermethylation on its promoter region. Synergy with a demethylator and histone deacetylase inhibitor or retinoids that stimulate retinoic acid receptor α induces endogenous occludin, which is sufficient for apoptotic sensitization. Our results show the functional diversity of occludin and suggest that methylator phenotype of occludin provides enhanced tumorigenic, invasive, and metastatic properties of cancer cells, identifying occludin as a likely candidate for a tumor-suppressor gene in certain types of cancer. (Cancer Res 2006; 66(18): 9125-33)
HBXIP, Cellular Target of Hepatitis B Virus Oncoprotein, Is a Regulator of Centrosome Dynamics and Cytokinesis
Authors: Fujii Ryoji , Zhu Changjun , Wen Yunfei , Marusawa Hiroyuki , Bailly-Maitre Beatrice , Matsuzawa Shu-ichi , Zhang Hong , Kim Youngsoo , Bennett C. Frank , Jiang Wei , Reed John C. 
Published: September 2006

AbstractHepatitis B virus accounts for more than 1 million cancer deaths annually, but the mechanism by which this virus promotes hepatocellular carcinoma remains unclear. The hepatitis B virus genome encodes an oncoprotein, HBx, which binds various cellular proteins including HBXIP. We show here that HBXIP is a regulator of centrosome duplication, required for bipolar spindle formation in HeLa human carcinoma cells and primary mouse embryonic fibroblast cells. We found that most cells deficient in HBXIP arrest in prometaphase with monopolar spindles whereas HBXIP overexpression causes tripolar or multipolar spindles due to excessive centrosome replication. Additionally, a defect in cytokinesis was seen in HBXIP-deficient HeLa cells, with most cells failing to complete division and succumbing eventually to apoptosis. Expression of viral HBx in HeLa cells mimicked the effects of HBXIP overexpression, causing excessive centrosome replication, resulting in tripolar and multipolar spindles and defective cytokinesis. Immunolocalization and fluorescent protein tagging experiments showed that HBXIP associates with microtubules of dividing cells and colocalizes with HBx on centrosomes. Thus, viral HBx and its cellular target HBXIP regulate centrosome dynamics and cytokinesis affecting genetic stability. In vivo experiments using antisense oligonucleotides targeting HBXIP in a mouse model of liver regeneration showed a requirement for HBXIP for growth and survival of replicating hepatocytes. Thus, HBXIP is a critical regulator of hepatocyte cell growth in vivo, making it a strong candidate for explaining the tumorigenic actions of viral HBx. (Cancer Res 2006; 66(18): 9099-107)
MCT-1 Protein Interacts with the Cap Complex and Modulates Messenger RNA Translational Profiles
Authors: Reinert Line S. , Shi Bo , Nandi Suvobroto , Mazan-Mamczarz Krystyna , Vitolo Michele , Bachman Kurtis E. , He Huili , Gartenhaus Ronald B. 
Published: September 2006

Abstract
MCT-1 is an oncogene that was initially identified in a human T cell lymphoma and has been shown to induce cell proliferation as well as activate survival-related pathways. MCT-1 contains the PUA domain, a recently described RNA-binding domain that is found in several tRNA and rRNA modification enzymes. Here, we established that MCT-1 protein interacts with the cap complex through its PUA domain and recruits the density-regulated protein (DENR/DRP), containing the SUI1 translation initiation domain. Through the use of microarray analysis on polysome-associated mRNAs, we showed that up-regulation of MCT-1 was able to modulate the translation profiles of BCL2L2, TFDP1, MRE11A, cyclin D1, and E2F1 mRNAs, despite equivalent levels of mRNAs in the cytoplasm. Our data establish a role for MCT-1 in translational regulation, and support a linkage between translational control and oncogenesis. (Cancer Res 2006; 66(18): 8994-9001)
Measures of scale based on the wavelet scalogram with applications to seismic attenuation
Authors: Li Hongbing , Zhao Wenzhi , Cao Hong , Yao Fengchang , Shao Longyi 
Published: September 2006

The attenuation of seismic signal is usually characterized in the frequency domain using Fourier power spectra and is often usefully characterized by average measures, such as the center frequency or spectral mean. Fourier analysis, however, suffers from time-frequency resolution problems. Wavelet analysis has better time-frequency localization and offers superior spectral decomposition. In this paper, we show that seismic attenuation can be characterized by the scalogram (also called energy density) in the wavelet domain. A single scale encompasses a frequency band. The scalogram relates absorption to peak-scale variations. The peak scale is the scale of maximum amplitude in the scalogram. Seismic attenuation can be estimated directly from the scalogram according to the scale shift of the data and can also be described indirectly by the centroid of scale (the mean of a scalogram).In absorbing media, seismic attenuation increases with frequency, i.e., decreases with scale. In the wavelet domain, small-scale energies of the seismic signal are attenuated more rapidly than are large-scale energies as waves propagate. As a result, both the peak scale and the centroid of the signal’s scalogram increase during propagation. Under the assumption of a frequency-independent [Formula: see text] model, these increases of the peak scale and the centroid of scale are inversely proportional to the quality factor, i.e., a lower quality factor results in an upshift of the peak scale in the scalogram and an increase of the centroid of scale. The peak-scale-shift method can be applied to seismic data with sufficiently broad signal bandwidth. The centroid of scale can be used as an attribute to qualitatively characterize seismic attenuation. Examples of gas detection in both synthetic and field data show the value of this technique.
Wavefield and AVO modeling using elastic thin-slab method
Authors: Wu Xian-Yun , Wu Ru-Shan 
Published: September 2006

We propose a dual-domain, one-way, elastic thin-slab method for fast and accurate amplitude variation with offset (AVO) modeling. In this method, the wavefield propagates in the wavenumber domain and interacts with heterogeneity in the space domain. The approach requires much less memory and is two to three orders of magnitude faster than a full-wave method using finite difference or finite element.The thin-bed AVO and AVOs with lateral parameter variations have been conducted using the thin-slab method and compared with reflectivity and finite-difference methods, respectively. It is shown that the thin-slab method can be used to accurately model reflections for most sedimentary rocks that have intermediate parameter perturbations ([Formula: see text] for P-wave velocity and [Formula: see text] for S-wave velocity). The combined effects of overburden structure and the scattering associated with heterogeneities on AVO have been investigated using the thin-slab method. Properties of the target zone and overburden structure control the AVO trends at overall offsets. Scattering associated with heterogeneities increases local variance in the reflected amplitudes and becomes significant for the sedimentary models with weak reflections. Interpretation of AVO observations based on homogeneous elastic models would therefore bias the estimated properties of the target. Furthermore, these effects can produce different apparent AVO trends in different offset ranges.
3D seismic refraction traveltime tomography at a groundwater contamination site
Authors: Zelt Colin A. , Azaria Aron , Levander Alan 
Published: September 2006

We have applied traveltime tomography to 3D seismic refraction data collected at Hill Air Force Base, Utah, in an approximately [Formula: see text] area over a shallow [Formula: see text] groundwater contamination site. The purpose of this study is to test the ability of 3D first-arrival-time data to characterize the shallow environment and aid remediation efforts. The aquifer is bounded below by a clay aquiclude, into which a paleochannel has been incised and acts as a trap for dense nonaqueous phase liquid (DNAPL) contaminants. A regularized nonlinear tomographic approach was applied to [Formula: see text] first-arrival traveltimes to obtain the smoothest minimum-structure 3D velocity model. The resulting velocity model contains a velocity increase from less than [Formula: see text] in the upper [Formula: see text]. The model also contains a north-south-trending low-velocity feature interpreted to be the paleochannel, based on more than 100 wells in the area. Checkerboard tests show [Formula: see text] lateral resolution throughout most of the model. The preferred final model was chosen after a systematic test of the free parameters involved in the tomographic approach, including the starting model. The final velocity model compares favorably with a 3D poststack depth migration and 2D waveform inversion of coincident reflection data. While the long-wavelength features of the model reveal the primary target of the survey, the paleochannel, the velocity model is likely a very smooth characterization of the true velocity structure, particularly in the vertical direction, given the size of the first Fresnel zone for these data.
Small-angle AVO response of PS-waves in tilted transversely isotropic media
Authors: Behura Jyoti , Tsvankin Ilya 
Published: September 2006

Field records for small source-receiver offsets often contain intensive converted PS-waves that may be caused by the influence of anisotropy on either side of the reflector. Here, we study the small-angle reflection coefficients of the split converted [Formula: see text]- and [Formula: see text]-waves ([Formula: see text] and [Formula: see text]) for a horizontal interface separating two transversely isotropic (TI) media with arbitrary orientations of the symmetry axis. The normal-incidence reflection coefficients [Formula: see text] and [Formula: see text] vanish when both half-spaces have a horizontal symmetry plane, which happens if the symmetry axis is vertical or horizontal (i.e., if the medium is VTI or HTI). For a tilted symmetry axis in either medium, however, the magnitude of the reflection coefficients can reach substantial values that exceed 0.1, even if the anisotropy strength is moderate. To study the influence exerted by the orientation of the symmetry axis and the anisotropy parameters, we develop concise weak-contrast, weak-anisotropyapproximations for the PS-wave reflection coefficients and com-pare them with exact numerical results. In particular, the analytic solutions show that the contributions made by the Thomsen parameters [Formula: see text] and [Formula: see text] and the symmetry-axis tilt [Formula: see text] to the coefficients [Formula: see text] and [Formula: see text] can be expressed through the first derivative of the P-wave phase velocity at normal incidence. If the symmetry-axis orientation and anisotropy parameters do not change across the interface, the normal-incidence reflection coefficients are insignificant, regardless of the strength of the velocity and density contrast. The AVO (amplitude variation with offset) gradients of the PS-waves are influenced primarily by the anisotropy of the incidence medium that causes shear-wave splitting and determines the partitioning of energy between the [Formula: see text] and [Formula: see text] modes. Because of their substantial amplitude, small-angle PS reflections in TI media contain valuable information for anisotropic AVO inversion of multicomponent data. Our analytic solutions provide a foundation for linear AVO-inversion algorithms and can be used to guide nonlinear inversion that is based on the exact reflection coefficients.
Q(z) model building using walkaway VSP data
Authors: Guerra Rafael , Leaney Scott 
Published: September 2006

Advanced seismic processing applications that use inverse [Formula: see text]-filtering for enhanced seismic resolution and true amplitude processing require reliable [Formula: see text] earth models. While interval [Formula: see text] may be accurately estimated by zero offset VSP surveys, quality data are obtained over relatively limited depth intervals, and shallower well sections pose special problems because of hole size, multiple casings, and lack of cementation. To obtain a more complete [Formula: see text] model, we have developed a theoretical method for combining zero offset VSP [Formula: see text] measurements with either effective-[Formula: see text] measurements from walkaway VSP surveys or surface seismic common midpoint (CMP) gathers. Using a simple crustal model of isotropic and homogenous flat layers, we derive an analytical result for the effective-[Formula: see text] measured from walkaway VSP surveys or from CMP gathers. We have found that effective-[Formula: see text] approaches a weighted harmonic mean ⟨[Formula: see text] of the overburden interval [Formula: see text]-values for short source-receiver offsets. This new method allows [Formula: see text] models to be constructed from the surface down to the total depth of the well, or even deeper, by combining offset-dependent effective-[Formula: see text] measurements with depth-dependent interval [Formula: see text] estimates from zero-offset VSP. The technique is also a simple method of compensating surface seismic gathers for anelastic [Formula: see text] absorption in an offset-dependent and time-variant way. We tested our new method using both synthetic data and walkaway and zero-offset VSP field data from the North Sea.