Combining Transfer of TTF-1 and Pax-8 Gene: a Potential Strategy to Promote Radioiodine Therapy of Thyroid Carcinoma

Cotransfer of TTF-1 and Pax-8 gene to tumor cells, resulting in the reexpression of iodide metabolism-associated proteins, such as sodium iodide symporter (NIS), thyroglobulin (Tg), thyroperoxidase (TPO), offers the possibility of radioiodine therapy to non-iodide-concentrating tumor because the expression of iodide metabolism-associated proteins in thyroid are mediated by the thyroid transcription factors TTF-1 and Pax-8. The human TTF-1 and Pax-8 gene were transducted into the human thyroid carcinoma (K1 and F133) cells by the recombinant adenovirus, AdTTF-1 and AdPax-8. Reexpression of NIS mRNA and protein, but not TPO and Tg mRNA and protein, was detected in AdTTF-1-infected F133 cells, following with increasing radioiodine uptake (6.1~7.4 times), scarcely iodide organification and rapid iodide efflux (t1/2≈8 min in vitro, t1/2≈4.7 h in vivo).
In contrast, all of the reexpression of NIS, TPO and Tg mRNA and proteins in F133 cells were induced by the synergetic effect of TTF-1 and Pax-8. AdTTF-1 and AdPax-8 coinfected K1 and F133 cells could effectively accumulate radioiodine (6.6-7.5 times) and obviously retarded radioiodine retention (t1/2≈25-30 min in vitro, t1/2≈12 h in vivo) (p<0.05).
Accordingly, the effect of radioiodine therapy of TTF-1 and Pax-8 cotransducted K1 and
F133 cells (21-25% survival rate in vitro) was better than that of TTF-1-transducted cells
(40% survival rate in vitro) (p<0.05). These results indicate that single TTF-1 gene transfer may have limited efficacy of radioiodine therapy because of rapid radioiodine efflux. The cotransduction of TTF-1 and Pax-8 gene, with resulting NIS-mediated radioiodine accumulation and TPO and Tg-mediated radioiodine organification and intracellular retention, may lead to effective radioiodine therapy of thyroid carcinoma

Methodological quality of all eligible studies.

<p>Each item is presented as percentages across all included studies.</p

Flow chart showing the process of study selection.

<p>Flow chart showing the process of study selection.</p

The diagnostic accuracy of PET/MRI for detection of malignant lesions.

<p>The diagnostic accuracy of PET/MRI for detection of malignant lesions.</p

Diagnostic Performance of Whole-Body PET/MRI for Detecting Malignancies in Cancer Patients: A Meta-Analysis - Fig 4

<p>Deeks funnel plot of asymmetry test for publication bias on a per-patient level (a) and a per-lesion level (b). The nonsignificant slope indicates the absence of publication bias.</p

The principal characteristics of included studies.

<p>The principal characteristics of included studies.</p

Genomic analysis of bacteriophage ϕAB1, a ϕKMV-like virus infecting multidrug-resistant Acinetobacter baumannii

AbstractWe present the complete genomic sequence of a lytic bacteriophage ϕAB1 which can infect many clinical isolates of multidrug-resistant Acinetobacter baumannii. The recently isolated bacteriophage displays morphology resembling Podoviridae family. The ϕAB1 genome is a linear double-stranded DNA of 41,526bp containing 46 possible open reading frames (ORFs). The majority of the predicted structural proteins were identified as part of the phage particle by mass spectrometry analysis. According to the virion morphology, overall genomic structure, and the phylogenetic tree of RNA polymerase, we propose that ϕAB1 is a new member of the ϕKMV-like phages. Additionally, we identified four ORFs encoding putative HNH endonucleases, one of which is presumed to integrate and create a genes-in-pieces DNA polymerase. Also, a potential lysis cassette was identified in the late genome. The lytic power of this bacteriophage combined with its specificity for A. baumannii makes ϕAB1 an attractive agent for therapeutic or disinfection applications