HSF1 overexpression enhances oncolytic effect of replicative adenovirus

<p>Abstract</p> <p>Background</p> <p>E1B55kD deleted oncolytic adenovirus was designed to achieve cancer-specific cytotoxicity, but showed limitations in clinical study. To find a method to increase its efficacy, we investigated the correlation between oncolytic effect of such oncolytic adenovirus Adel55 and intracellular heat shock transcription factor 1 (HSF1) activity.</p> <p>Methods</p> <p>In the present study, human breast cancer cell line Bcap37 was stably transfected with constitutively active HSF1 (cHSF1) or HSF1 specific siRNA (HSF1i) to establish increased or decreased HSF1 expression levels. Cytotoxicity of Adel55 was analyzed in these cell lines <it>in vitro </it>and <it>in vivo</it>. Furthermore, Adel55 incorporated with cHSF1 (Adel55-cHSF1) was used to treat various tumor xenografts.</p> <p>Results</p> <p>Adel55 could achieve more efficient oncolysis in cHSF1 transfected Bcap37 cells, both <it>in vitro </it>and <it>in vivo</it>. However, inhibition of HSF1 expression by HSF1i could rescue Bcap37 cell line from oncolysis by Adel55. A time course study of viral replication established a correlation between higher replication of Adel55 and cytolysis or tumor growth inhibition. Then, we constructed Adel55-cHSF1 for tumor gene therapy and demonstrated that it is more potent than Adel55 itself in oncolysis and replication in both Bcap37 and SW620 xenografts.</p> <p>Conclusions</p> <p>cHSF1 enhances the Adel55 cell-killing potential through increasing the viral replication and is a potential therapeutic implication to augment the potential of E1B55kD deleted oncolytic adenovirus by increasing its burst.</p

An integrated chromatin accessibility and transcriptome landscape of human pre-implantation embryos

Early human embryonic development involves extensive changes in chromatin structure and transcriptional activity. Here the authors present LiCAT-seq, a method enabling simultaneous profiling of chromatin accessibility and gene expression with ultra-low input of cells and map chromatin accessibility and transcriptome landscapes for human pre-implantation embryos

Screening ethnically diverse human embryonic stem cells identifies a chromosome 20 minimal amplicon conferring growth advantage

The International Stem Cell Initiative analyzed 125 human embryonic stem (ES) cell lines and 11 induced pluripotent stem (iPS) cell lines, from 38 laboratories worldwide, for genetic changes occurring during culture. Most lines were analyzed at an early and late passage. Single-nucleotide polymorphism (SNP) analysis revealed that they included representatives of most major ethnic groups. Most lines remained karyotypically normal, but there was a progressive tendency to acquire changes on prolonged culture, commonly affecting chromosomes 1, 12, 17 and 20. DNA methylation patterns changed haphazardly with no link to time in culture. Structural variants, determined from the SNP arrays, also appeared sporadically. No common variants related to culture were observed on chromosomes 1, 12 and 17, but a minimal amplicon in chromosome 20q11.21, including three genes expressed in human ES cells, ID1, BCL2L1 and HM13, occurred in >20% of the lines. Of these genes, BCL2L1 is a strong candidate for driving culture adaptation of ES cells