Interleukin 6 enhances a cellular activity that functionally substitutes for E1A protein in transactivation.

Spergel, Jonathan M.; Chen‐Kiang, Selina

doi:10.1073/pnas.88.15.6472

Cited by 55 publications

(37 citation statements)

References 40 publications

(30 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This result confirms earlier findings of residual expression of adenoviral genes such as E2, E3 and E4, [2][3][4] whose promotors are active at higher MOIs. Not surprisingly, a low level of replication of E1-deleted vectors in target cells under certain circumstances and in certain cell lines has been reported in vitro 28 and in vivo. 4 We were able to confirm adenoviral replication in HepG2 cells and extend this finding to all three other cell lines (A2, HuH7, A549) examined.…”

Section: Discussionmentioning

confidence: 99%

Induction of apoptosis and G2/M arrest by infection with replication-deficient adenovirus at high multiplicity of infection

et al. 1999

View full text Add to dashboard Cite

Replication-deficient adenoviruses are among the most widely used vectors in gene therapy and are also becoming increasingly popular as analytical tools in basic research. However, significant toxicity of these vectors in vivo has been reported. Here, we show that in an in vitro setting, first generation adenoviruses lead to growth retardation, prolongation of the G2/M phase and induction of apoptosis if applied at a high multiplicity of infection (MOI). These findings were obtained in p53-deficient hepatocytes, derived from knock-out mice (A2 cells) and in several tumor cell lines containing wild-type (wt) or mutant p53. Apoptosis induction was correlated with increased levels of p53 and bax proteins and it was stronger in cells containing wt p53 as compared with cells lacking functional p53. Apoptosis was highly dependent on the MOI used with marked effects starting at an MOI twice as high as needed for 100 % gene transfer. Expression of the adenoviral E4 ORF6 gene as well as adenoviral replication were detected in all cell lines infected with first generation adenovirus. Apoptosis could be considerably reduced but not abrogated by UV inactivation of adenovirus, which indicates proapoptotic effects caused by the infection event as well as by residual adenoviral gene expression or adenoviral replication. First generation adenoviruses apparently display proapoptotic activity if used at higher MOIs, which may be of relevance when these vectors are used as analytical or gene therapeutic tools

show abstract

Section: Discussionmentioning

confidence: 99%

Induction of apoptosis and G2/M arrest by infection with replication-deficient adenovirus at high multiplicity of infection

et al. 1999

View full text Add to dashboard Cite

show abstract

“…14,15 It was demonstrated earlier that cellular transcription factors can functionally substitute E1A in its transactivator function, which makes the E2 and the E4 promoter potential candidates for interference. [15][16][17] The pIX promoter is orientated rightwards with respect to the viral genome and is located directly adjacent to the E1 insertion site for transgene cassettes. Besides enhancers that act distance and orientation independent, viral sequences contain transcription factor binding sites that represent upstream regulatory elements (UREs).…”

Section: Introductionmentioning

confidence: 99%

Insulation from viral transcriptional regulatory elements improves inducible transgene expression from adenovirus vectors in vitro and in vivo

2000

View full text Add to dashboard Cite

“…This phenomenon has been reported before with the presence of IL-6 or papillomavirus E6 and E7 allowing replication of E1-deleted viruses. [60][61][62][63][64] In fact, it was demonstrated that factors produced by primary ovarian cancer cells allowed similar replication of an E1-deleted virus and a wild-type adenovirus. 60 While xenografts have traditionally been utilized for investigation of therapeutic efficacy, receptor levels on these cancer cell lines may not correspond well with primary tumors.…”

Section: Discussionmentioning

confidence: 99%

Replication of an integrin targeted conditionally replicating adenovirus on primary ovarian cancer spheroids

et al. 2003

View full text Add to dashboard Cite

Replication competent viruses hold promise for treatment of advanced cancers resistant to available therapeutic modalities. Although preliminary clinical results have substantiated their efficacy, preclinical development of these novel approaches is limited by assay substrates. The evaluation of candidate agents could be confounded by differences between primary tumor cells and tumor cell lines, as discordance in the levels of surface receptors relevant for viral entry has been reported. Since primary tumor cells are difficult to analyze ex vivo for longitudinal observation of virus replication, we developed three-dimensional aggregates or spheroids of unpassaged and purified ovarian cancer cells as a means for prolonging primary tumor cell viability and as a threedimensional in vitro model for replicative viral infection. Ovarian cancer cells purified from ascites samples were sustained for 30 days while retaining the infection profile with tropism modified and unmodified adenoviruses (Ads). Cell line and primary cell spheroids were used to quantitate the replication and oncolytic potency of replicative Ads in preclinical testing for human ovarian cancer trials. Therefore, spheroids provide a method to sustain purified unpassaged primary ovarian cancer cells for extended periods and to allow evaluation of replicative viruses in a three-dimensional model.

show abstract

Interleukin 6 enhances a cellular activity that functionally substitutes for E1A protein in transactivation.

Cited by 55 publications

References 40 publications

Induction of apoptosis and G2/M arrest by infection with replication-deficient adenovirus at high multiplicity of infection

Induction of apoptosis and G2/M arrest by infection with replication-deficient adenovirus at high multiplicity of infection

Insulation from viral transcriptional regulatory elements improves inducible transgene expression from adenovirus vectors in vitro and in vivo

Replication of an integrin targeted conditionally replicating adenovirus on primary ovarian cancer spheroids

Contact Info

Product

Resources

About