Abstract
We evaluated 22 hepatocyte-specific expression cassettes containing a human apo A-I transgene following hydrodynamic transfer of plasmids or adenoviral transfer with E1E3E4-deleted vectors in C57BL/6 mice. The DC172 promoter consisting of a 890 bp human alpha(1)-antitrypsin promoter and two copies o...
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PMID: 18288213
PDF is available here.
Abstract
We have observed that Ad5 mutants with large deletions in E3 that infringe on the U exon display a mild growth defect, as well as an aberrant Ad E2 DNA-binding protein (DBP) intranuclear localization pattern and an apparent failure to organize replication centers during late infection. Mutants in wh...
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PMID: 17881437
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Klaus K Mantwill,
Nadia N Köhler-Vargas,
Alexandra A Bernshausen,
Alexa A Bieler,
Hermann H Lage,
Alexander A Kaszubiak,
Pavel P Surowiak,
Tanja T Dravits,
Uwe U Treiber,
Rudolf R Hartung,
Bernd B Gansbacher and
Per S PS Holm
Abstract
We report that an oncolytic adenovirus, named Xvir03, expressing the viral proteins E1B55k and E4orf6, leads to nuclear translocation of YB-1 and in consequence to viral replication and cell lysis in vitro and in vivo. Moreover, we show that Xvir03 down-regulates the expression of MDR1 and MRP1, ind...
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PMID: 16849566
PDF is available here.
Abstract
We applied p53-null Hep3B and Saos2 cells as models to clarify the replication ability of E1B55K-deleted adenoviruses with different expression levels of E1a. We show that lower E1A expression in Saos2 may be the reason for the poor replication in some cancer cells due to the fact that E1a promoter...
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PMID: 16341141
PDF is available here.
Abstract
Our data establishes the contribution of the transcription-independent mitochondrial p53 pathway to apoptosis of primary cells in response to deregulated oncogenes....
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PMID: 16226255
PDF is available here.
Abstract
We developed a novel adenovirus-based amplicon with an Epstein-Barr virus origin of replication, Ad type 5 (Ad5) inverted terminal repeats, all Ad5 early region 2 (E2) genes, and the early region 4 (E4) open reading frame 6 (ORF6) under the control of a tetracycline-dependent promoter. The amplicon...
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PMID: 15858023
PDF is available here.
Abstract
We measured rates during the production of adenovirus vectors with genomes containing three different expression cassette arrangements. The vectors had different extents of sequence identity with integrated Ad5 DNA of 293 cells and had different distributions of identity flanking the expression cass...
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PMID: 15827158
PDF is available here.
Abstract
Historically, the adenoviral E3 region was found to be nonessential for viral replication in vitro. In addition, adenoviruses whose genome was more than approximately 105% the size of the native genome were inefficiently packaged. These profound observations were used experimentally to insert transg...
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PMID: 15827160
PDF is available here.
Abstract
Adenovirus (Ad) gene therapy vectors made replication defective by deletion of the E1 region (first-generation vectors) induce high-level inflammation that leads to loss of both transduced gene expression and transduced cells. First-generation vectors were initially considered to be incapable of vir...
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PMID: 15769613
PDF is available here.
Abstract
We investigated AAV's interaction with adenovirus (Ad), AAV's most efficient helper virus. Coinfection with Ad and AAV results in an AAV-mediated inhibition of Ad5 gene expression and replication. The AAV replication proteins (Rep) activate and repress gene expression from AAV and heterologous trans...
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PMID: 15596798
PDF is available here.
Abstract
We examined the molecular mechanisms mediating these two different cellular responses to p16 overexpression. Ectopic expression of p16 leads to G1 arrest in NP-9 cells by redistributing p21/p27 CKIs and inhibiting cyclin-dependent kinase CDK2 activity. In contrast, in NP-18 cells cyclin E (CycE)/CDK...
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PMID: 15309028
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Abstract
We have expressed the prodrug-activating enzyme nitroreductase (NTR) in the context of an E1B-55K-deleted adenovirus, CRAd-NTR(PS1217H6). We show that CRAd-NTR(PS1217H6) retains oncolytic growth properties, and expresses substantially more NTR than a comparable, replication-defective adenovirus. The...
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PMID: 15164095
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Abstract
We have identified the bromodomain protein Brd4 as a major cellular interacting partner of the bovine papillomavirus E2. Brd4 associates with mitotic chromosomes and colocalizes with E2 on mitotic chromosomes. The site of E2 binding maps to the C-terminal domain of Brd4. Expression of this C-termina...
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PMID: 15109495
PDF is available here.
Abstract
We report here on the properties of oncolytic adenoviruses which contain the luciferase cDNA fused via an optimized internal ribosome entry site (IRES) to the immediate early adenoviral gene E1A (AdDeltaE1AIL), the early gene E2B (AdDeltaE2BIL), or the late fiber gene (AdDeltafiberIL). These viruses...
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PMID: 15003868
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Abstract
We utilized a screening method to search for genes within the OAdV genome that were capable of stimulating the viral E2 promoter. One such gene, E43, was identified within the proposed E4 region toward the right-hand end of the OAdV genome. The E43 gene product was also found to be capable of stimul...
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PMID: 14972537
PDF is available here.
Abstract
We identified several novel BRG1-regulated genes. Our work provides further evidence for a role for BRG1 in the regulation of several genes involved in key steps in tumorigenesis and has revealed a potential mechanism for BRG1-induced growth arrest....
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PMID: 14673169
PDF is available here.
Abstract
We have examined the subcellular localization properties of human adenovirus 2 (HAdV-2) preMu and mature Mu (pX) proteins as fusions with enhanced green fluorescence protein (EGFP). We determined that preMu is exclusively a nucleolar protein with a single nucleolar accumulation signal within the Mu...
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PMID: 14718634
PDF is available here.
Abstract
We have examined the properties of the small E2E RNAs and E2E RNA polymerase III transcription in more detail. The accumulation of cytoplasmic E2E RNAs and the rates of E2E transcription by the two RNA polymerases during the infectious cycle were analyzed by using RNase T(1) protection and run-on tr...
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PMID: 12634361
PDF is available here.
Abstract
We therefore investigated the effects of atorvastatin on minichromosome maintenance (MCM) protein 6 and 7 expression in vascular smooth muscle cells, two proteins essential for initiation of DNA replication. Stimulation of quiescent rat aortic vascular smooth muscle cells with fetal bovine serum ind...
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PMID: 12591091
PDF is available here.
Abstract
Our results suggest that APC functions upstream of RB in the G(1)/S regulatory pathway, cyclin D1 and cMYC affect APC-mediated arrest equivalently to oncogenic beta-catenin, and most colon tumors disrupt control of G(1)/S progression by APC mutation....
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PMID: 12198702
PDF is available here.
Abstract
Most if not all neoplasias show a directly or indirectly deregulated cell cycle. Targeting its regulatory molecules, the cyclin-dependent kinases, as a therapeutic mode to develop new anticancer drugs, is being currently explored in both academia and pharmaceutical companies. The development of new...
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PMID: 12107831
PDF is available here.
Abstract
We investigate Rep-mediated effects on expression of the adenovirus (Ad) E2a gene and the Ad major late promoter. We have found that all four Rep proteins repress E2a expression at the protein level, with Rep40 showing the weakest repression. Mutations in the purine nucleotide binding (PNB) site wea...
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PMID: 11886255
PDF is available here.
Shuhei S Nishiguchi,
Masaru M Enomoto,
Susumu S Shiomi,
Noriko N Obata,
Motoharu M Tanaka,
Katsuhiko K Fukuda,
Akihiro A Tamori,
Daiki D Habu,
Tadashi T Takeda,
Takashi T Tanaka,
Yoshihisa Y Yano and
Shuzo S Otani
Abstract
The association of the newly identified viruses, GB virus C (GBV-C) and TT virus (TTV), with autoimmune hepatitis remains to be elucidated. Sera from 20 Japanese patients with autoimmune hepatitis and 50 volunteer blood donors were assayed for GBV-C RNA, antibodies to the GBV-C second envelope prote...
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PMID: 11782937
PDF is available here.
Abstract
We demonstrate in this study the great degree of specificity in peptides selected by a class II MHC molecule during processing. In this specific case of the diabetogenic I-A(g7) molecule, the P9 pocket of I-A(g7) plays a critical role in determining the final outcome of epitope selection, a conclusi...
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PMID: 11801660
PDF is available here.
Abstract
We have begun an investigation into AAV's relationship with adenovirus (Ad), AAV's most efficient helper virus. AAV, but not UV-inactivated AAV, delayed Ad-induced cytotoxicity and inhibited Ad E2a gene expression. AAV, but not UV-inactivated AAV or a recombinant AAV vector, inhibited Ad DNA replica...
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PMID: 11878883
PDF is available here.
Abstract
BACKGROUND: The aim was to estimate the prevalence and the persistence of GB virus C/hepatitis G virus (GBV-C/HGV) exposure markers in a group at high risk for transfusion-transmitted agents. PATIENTS AND METHODS: Serum samples from 37 thalassemic patients were screened for GBV-C/HGV RNA by reverse...
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PMID: 11545484
PDF is available here.
Abstract
We created transgenic mice expressing a DNA binding mutant of tal-1. Surprisingly, these mice develop disease, demonstrating that the DNA binding properties of tal-1 are not required to induce leukemia/lymphoma in mice. However, wild type tal-1 and the DNA binding mutant both form stable complexes w...
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PMID: 11439353
PDF is available here.
Abstract
We show here that E1A12S binds to the regulatory subunits (R) of PKA in vitro and in vivo. Interaction depends on the N-terminus and the conserved region 1 (CR1) of E1A12S. Both domains are also essential for the activation of viral E2 gene expression. Infection of cells with Ad12 leads to the cellu...
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PMID: 11414803
PDF is available here.
Abstract
DNA sequence coding for a portion of DNA binding protein (amino acids 3-58) of bovine adenovirus type-3 (BAV-3) was cloned and expressed in Escherichia coli as a fusion protein with Schistosoma japonicum glutathione S-transferase. The fusion protein was affinity purified and used to immunize rabbits...
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PMID: 11337049
PDF is available here.
Abstract
We attenuated viral gene expression by eliminating E1, E2a, E3, and E4 early genes from the adenoviral backbone. Two highly attenuated, fourth-generation (Av4) E1/E2a/E3/E4-deficient adenoviral vectors encoding human factor VIII (FVIII) under the control of a liver-specific albumin promoter were gen...
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PMID: 11273775
PDF is available here.
Abstract
The inverted terminal repeat (ITR) of the genome of four bovine adenovirus (BAdV) types have been sequenced, analysed and compared to the ITRs of other adenoviruses. The length of ITRs of the examined BAdVs ranged between 59 and 368 base pairs, thus the presently known longest adenovirus ITR sequenc...
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PMID: 11324754
PDF is available here.
Abstract
The complete nucleotide sequence of porcine adenovirus serotype 5 (PAdV-5) has been determined and the putative genomic map was constructed. The size of the genome was found to be 32621 nucleotides. Twenty-eight putative ORFs were identified by their homology to other adenovirus or other virus and e...
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PMID: 11172093
PDF is available here.
Abstract
We have developed replicating adenoviruses that express the viral E1B and E2 genes from promoters controlled by the Tcf4 transcription factor. Tcf4 is constitutively activated by mutations in the adenomatous polyposis coli and beta-catenin genes in virtually all colon tumors and is constitutively re...
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PMID: 11222711
PDF is available here.
Abstract
Overall, these results indicate that chronic infection by HCV is associated with an allostimulatory defect of monocyte-derived DC, possibly because these cells constitute an extrahepatic reservoir for the virus. Although the exact mechanism responsible for such an alteration remains to be unraveled,...
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PMID: 11159892
PDF is available here.
Abstract
To identify and characterize the protein encoded by the E2A region of porcine adenovirus (PAV)-3, DNA sequence coding for a portion (amino acids 102-457) of the DNA binding protein (DBP) open reaching frame was cloned and expressed in Escherichia coli as a fusion protein with glutathione S-transfera...
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PMID: 11805441
PDF is available here.
Abstract
We now show that cultured adult rat sensory neurons can replicate DNA in response to ectopic expression of E2F1 or E2F2 and that this is augmented by expression of cyclin-dependent kinase activities. We also find that addition of serum and laminin inhibits the E2F-induced S-phase in neurons but not...
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PMID: 11149597
PDF is available here.
Abstract
We describe a new level of p300-dependent control mediated through the functional interaction between p300/CBP and members of the family of nucleosome assembly proteins (NAP), which includes NAP1, NAP2, and TAF1. We find that NAP proteins, which have previously been implicated in the regulation of t...
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PMID: 11073993
PDF is available here.
Abstract
We describe an improved genetic immunization strategy for eliciting a full spectrum of anti-hepatitis C virus (HCV) envelope 2 (E2) glycoprotein responses in mammals through electrical gene transfer (EGT) of plasmid DNA into muscle fibers. Intramuscular injection of a plasmid encoding a cross-reacti...
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PMID: 11090158
PDF is available here.
Abstract
These results provided a structural basis for the reactivity patterns of WH303 and also useful information for the design of a peptide containing this epitope for potential use in the detection and identification of CSFV. By deletion analysis, an antigenic domain capable of reacting with pig polyclo...
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PMID: 11090160
PDF is available here.
J P Gardner,
I Frolov,
S Perri,
Y Ji,
M L MacKichan,
J zur Megede,
M Chen,
B A Belli,
D A Driver,
S Sherrill,
C E Greer,
G R Otten,
S W Barnett,
M A Liu,
T W Dubensky and
J M Polo
Abstract
We derived variants of the prototype alphavirus, Sindbis virus (SIN), with differential abilities to infect human dendritic cells. Cloning and sequencing of the SIN variant genomes revealed that the genetic determinant for human dendritic cell (DC) tropism mapped to a single amino acid substitution...
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PMID: 11090185
PDF is available here.
Abstract
We observed that a second HPV-16 E2 C-terminal dimer can bind per DNA site at pH 7.0. This was confirmed by displacement of bis-ANS binding, tryptophan fluorescence, native electrophoresis, and circular dichroism. The two binding events are nonequivalent, with a high-affinity binding involving one E...
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PMID: 11087426
PDF is available here.
Abstract
Adenoviral vectors have been used in gene therapy and for vaccination. The major concerns with using adenoviral vectors are the pathogenic potential of the virus backbone and the generation of replication-competent adenovirus that may replicate in an uncontrolled manner, especially in immunocompromi...
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PMID: 10998335
PDF is available here.
Abstract
The prevalence of GB virus C (GBV-C)/ hepatitis G virus (HGV) RNA and antibodies to the structural E2 protein was investigated in a cohort of HIV-1 infected patients. Of 346 individuals, RNA was detected in 143 and E2 antibodies were detected in 73, for an overall prevalence of 62.4%. Intravenous dr...
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PMID: 11057510
PDF is available here.
Abstract
The modification of intracellular redox conditions with diethylmaleate (DEM), a glutathione-depleting agent, induces a p53-independent growth arrest mediated by the accumulation of p21(waf1) mRNA and protein. The same treatment also induces the retinoblastoma protein (pRb) dephosphorylation. This de...
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PMID: 10734236
PDF is available here.
Abstract
This study documents that stable rep-cap cells lines are severely hampered for rAAV assembly when a replicative adenovirus is substituted with an adenoviral plasmid. Furthermore, our results also suggest that the lack of amplification of the rep-cap genes, eventually combined with the altered distri...
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PMID: 10953917
PDF is available here.
Abstract
We characterize negative and positive regulatory sequences that flank the Pbx1 HD and determine their importance for myeloid immortalization by E2a-Pbx1. A 25 residue predicted alpha helix preceding the Pbx1 HD bound the HD and prevented both its binding to DNA and its ability to heterodimerize with...
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PMID: 10637514
PDF is available here.
Abstract
We cloned Ad5 E4orf6/7 cDNA in both simian virus 40- and human cytomegalovirus-based expression vectors to examine its transforming and apoptotic activities. The cloned E4orf6/7 collaborated with a retinoblastoma protein (RB)-nonbinding and therefore E2F-nonreleasing mutant of Ad5 E1A (dl922/947) to...
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PMID: 10559324
PDF is available here.
Abstract
Adenovirus-mediated E2F-1 gene transfer efficiently induces widespread apoptosis in human melanoma cells. E2F-1 overexpression induced apoptosis in cell lines containing wild-type and mutant p53, suggesting that this effect does not require wild-type p53 function. Anti-apoptotic proteins of the Bcl-...
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PMID: 10570427
PDF is available here.
Abstract
We have studied adenovirus-mediated cytotoxicity after infection of malignant cells obtained from patients with chronic lymphocytic leukemia (CLL). Our studies indicate that adenoviruses can infect primary CLL cells and that infection of CLL cells with a replication-competent strain of human adenovi...
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PMID: 10552960
PDF is available here.
Abstract
We report here a novel vector (Av4orf3nBg) lacking E1, E2a, and all of E4 except open reading frame 3 (ORF3) and expressing a beta-galactosidase reporter gene. This vector was generated by transfection of a plasmid carrying the full-length vector sequence into A30.S8 cells that express E1 and E2a bu...
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PMID: 10364357
PDF is available here.
Abstract
We generated transgenic mice expressing E2A-HLF using Ig enhancer and promoter, which direct transgene expression in cells committed to the lymphoid lineage. The transgenic mice exhibited abnormal development in the thymus and spleen and were susceptible to infection. The thymus contained small numb...
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PMID: 10216071
PDF is available here.
Abstract
We show that in transient transfection experiments, adenovirus E1A activation of the viral E2 promoter is abrogated by coexpression of the viral E4 open reading frame 4 (E4-ORF4) protein. This effect does not to require the retinoblastoma protein that previously has been shown to regulate E2F activi...
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PMID: 10191196
PDF is available here.
Abstract
We have identified a novel gene, FB1, by virtue of its fusion with E2A and by a combination of molecular techniques. FB1 was localized on 19q13.4, suggesting that the novel chimera originated by a cryptic rearrangement of chromosome 19. Two FB1 transcripts, of 1.2 kb and 1.1 kb, are differentially e...
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PMID: 10086727
PDF is available here.
Abstract
These results suggest that inactivation of the E4 promoter efficiently diminished the viral replication and the late viral gene expression, reduced host immune response and consequently reduced toxicity and prolonged the duration of transgene expression in vivo....
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PMID: 10435089
PDF is available here.
Abstract
We have observed the consequences of enforced expression of the E2A gene products E12 and E47 in cell lines derived from lymphomas that arose spontaneously in E2A-deficient mice. E2A-expressing cells are steadily eliminated from lymphoma cultures into which E47 or E12 was introduced. The mechanism u...
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PMID: 9927682
PDF is available here.
D D Duan,
P P Sharma,
L L Dudus,
Y Y Zhang,
S S Sanlioglu,
Z Z Yan,
Y Y Yue,
Y Y Ye,
R R Lester,
J J Yang,
K J KJ Fisher and
J F JF Engelhardt
Abstract
We have utilized a recombinant AAV (rAAV) shuttle vector to identify circular AAV intermediates from transduced HeLa cells and primary fibroblasts. The unique structural features exhibited by these transduction intermediates included circularized monomer and dimer virus genomes in a head-to-tail arr...
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PMID: 9847318
PDF is available here.
G G Teoh,
L L Chen,
M M Urashima,
Y T YT Tai,
L A LA Celi,
D D Chen,
D D Chauhan,
A A Ogata,
R W RW Finberg,
I J IJ Webb,
D W DW Kufe and
K C KC Anderson
Abstract
We have investigated the use of adenoviruses for the delivery of the thymidine kinase (tk) gene into multiple myeloma (MM) cells. We first demonstrated that MM cell lines and MM patient cells express both adenovirus receptors as well as the DF3/MUC1 protein, thus providing a rationale for using aden...
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PMID: 9845525
PDF is available here.
Abstract
The X-ray crystal structure of the DNA decamer d(GACCGCGGTC), containing half the human papilloma virus E2 binding site, has been solved from two crystals grown at different ionic conditions (50 mM MgCl2and 50 mM spermine or 1.56 mM MgCl2and 1.56 mM spermine). Despite the variation in salt concentra...
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PMID: 9838004
PDF is available here.