Viral markers in nasopharyngeal carcinoma: A systematic review and meta-analysis on the detection of p16INK4a, human papillomavirus (HPV), and Ebstein-Barr virus (EBV).

PURPOSE: This study aimed to conduct a meta-analysis to investigate the distribution of EBV and HPV stratified according to histological NPC type. MATERIALS & METHODS: We performed a meta-analysis to produce pooled prevalence estimates in a random-effects model. We also performed calculations for attributable fractions of viral combinations in NPC, stratified according to histological type. RESULTS: There was a higher prevalence of HPV DNA in WHO Type I (34.4%) versus WHO Type II/III (18.4%). The attributable fractions of WHO Type I NPC was predominantly double negative EBV(-) HPV(-) NPC (56.4%), and EBV(-) HPV(+) NPC (21.5%), in contrast to the predominant infection in WHO Type II/III which was EBV(+) HPV(-) NPC (87.5%). Co-infection of both EBV and HPV was uncommon, and double-negative infection was more common in WHO Type I NPC. CONCLUSION: A significant proportion of WHO Type I NPC was either double-negative EBV(-)HPV(-) or EBV(-)HPV(+).

Tbx2 mediates dorsal patterning and germ layer suppression through inhibition of BMP/GDF and Activin/Nodal signaling.

BACKGROUND: Members of the T-box family of DNA-binding proteins play a prominent role in the differentiation of the three primary germ layers. VegT, Brachyury, and Eomesodermin function as transcriptional activators and, in addition to directly activating the transcription of endoderm- and mesoderm-specific genes, serve as regulators of growth factor signaling during induction of these germ layers. In contrast, the T-box gene, tbx2, is expressed in the embryonic ectoderm, where Tbx2 functions as a transcriptional repressor and inhibits mesendodermal differentiation by the TGFß ligand Activin. Tbx2 misexpression also promotes dorsal ectodermal fate via inhibition of the BMP branch of the TGFß signaling network. RESULTS: Here, we report a physical association between Tbx2 and both Smad1 and Smad2, mediators of BMP and Activin/Nodal signaling, respectively. We perform structure/function analysis of Tbx2 to elucidate the roles of both Tbx2-Smad interaction and Tbx2 DNA-binding in germ layer suppression. CONCLUSION: Our studies demonstrate that Tbx2 associates with intracellular mediators of the Activin/Nodal and BMP/GDF pathways. We identify a novel repressor domain within Tbx2, and have determined that Tbx2 DNA-binding activity is required for repression of TGFß signaling. Finally, our data also point to overlapping yet distinct mechanisms for Tbx2-mediated repression of Activin/Nodal and BMP/GDF signaling.

Is human papillomavirus and p16 expression associated with survival outcomes in nasopharyngeal cancer?: A systematic review and meta-analysis.

INTRODUCTION: Human papillomavirus (HPV) is a known prognostic indicator in oropharyngeal cancer. Not much is known about the prognostic role of HPV in Nasopharyngeal cancer (NPC). Here, we performed a systematic review and meta-analysis of the literature to investigate if HPV status was a prognostic factor for NPC. METHODS: PubMed (via the web), Embase, Scopus, and the Cochrane Library were searched. A systematic review and meta-analysis was done to generate the pooled Hazard Ratios (HR) for Overall Survival (OS). RESULTS: A total of 7 studies from 2014 to 2018, reporting data on 2646 patients (range 43-1328) were included in this meta-analysis. The pooled data showed that HPV/p16 status was not associated with OS in NPC with HR of 0.77 (95% CI: 0.55-1.09, p = 0.14). The test for heterogeneity showed little to no heterogeneity of results (I2 = 4%, p = 0.38). Subgroup analysis showed that in large sample sizes, HPV was significantly associated with survival. CONCLUSION: Despite the finding in the pooled HR, we could not draw a definitive conclusion as to the prognostic significance of HPV in NPC. Recommendations for future research are given.

The red cell distribution width as a prognostic indicator in upper aerodigestive tract (UADT) cancer: A systematic review and meta-analysis.

PURPOSE: The aim of this systematic review and meta-analysis was to investigate the relationship between the Red Cell Distribution Width (RDW) and prognosis in upper aerodigestive tract (UADT) cancer. METHODS: PubMed (via the web), Embase, Scopus, and the Cochrane Library were searched. A systematic review and meta-analysis was done to generate the pooled hazard ratios (HR) for overall survival (OS), disease specific survival (DSS), and recurrence free survival (RFS). RESULTS: Our analysis included the results of 4200 patients in 8 cohorts. The pooled data demonstrated that an elevated RDW was associated with significantly poorer OS (HR: 1.44, 95% CI: 1.13-1.83), RFS (HR: 1.43, 95%CI: 1.13-1.82). The DSS result had high heterogeneity and 95% CI was not pooled. CONCLUSIONS: An elevated RDW may be an indicator of poor prognosis in UADT cancers in certain populations. Further research is needed to confirm this effect.

Tbx2 is required for the suppression of mesendoderm during early Xenopus development.

BACKGROUND: T-box family proteins are DNA-binding transcriptional regulators that play crucial roles during germ layer formation in the early vertebrate embryo. Well-characterized members of this family, including the transcriptional activators Brachyury and VegT, are essential for the proper formation of mesoderm and endoderm, respectively. To date, T-box proteins have not been shown to play a role in the promotion of the third primary germ layer, ectoderm. RESULTS: Here, we report that the T-box factor Tbx2 is both sufficient and necessary for ectodermal differentiation in the frog Xenopus laevis. Tbx2 is expressed zygotically in the presumptive ectoderm, during blastula and gastrula stages. Ectopic expression of Tbx2 represses mesoderm and endoderm, while loss of Tbx2 leads to inappropriate expression of mesoderm- and endoderm-specific genes in the region fated to give rise to ectoderm. Misexpression of Tbx2 also promotes neural tissue in animal cap explants, suggesting that Tbx2 plays a role in both the establishment of ectodermal fate and its dorsoventral patterning. CONCLUSIONS: Our studies demonstrate that Tbx2 functions as a transcriptional repressor during germ layer formation, and suggest that this activity is mediated in part through repression of target genes that are stimulated, in the mesendoderm, by transactivating T-box proteins. Taken together, our results point to a critical role for Tbx2 in limiting the potency of blastula-stage progenitor cells during vertebrate germ layer differentiation. Developmental Dynamics 247:903-913, 2018. © 2018 Wiley Periodicals, Inc.

Xmab21l3 mediates dorsoventral patterning in Xenopus laevis.

Specification of the dorsoventral (DV) axis is critical for the subsequent differentiation of regional fate in the primary germ layers of the vertebrate embryo. We have identified a novel factor that is essential for dorsal development in embryos of the frog Xenopus laevis. Misexpression of Xenopus mab21-like 3 (Xmab21l3) dorsalizes gastrula-stage mesoderm and neurula-stage ectoderm, while morpholino-mediated knockdown of Xmab21l3 inhibits dorsal differentiation of these embryonic germ layers. Xmab21l3 is a member of a chordate-specific subclass of a recently characterized gene family, all members of which contain a conserved, but as yet ill-defined, Mab21 domain. Our studies suggest that Xmab21l3 functions to repress ventralizing activity in the early vertebrate embryo, via regulation of BMP/Smad and Ras/ERK signaling.

Measuring the rate of conjugal plasmid transfer in a bacterial population using quantitative PCR.

Horizontal transfer of genes between species is an important mechanism for bacterial genome evolution. In Escherichia coli, conjugation is the transfer from a donor (F(+)) to a recipient (F(-)) cell through cell-to-cell contact. We demonstrate what we believe to be a novel qPCR method for quantifying the transfer kinetics of the F plasmid in a population by enumerating the relative abundance of genetic loci unique to the plasmid and the chromosome. This approach allows us to query the plasmid transfer rate without the need for selective culturing with unprecedented single locus resolution. We fit the results to a mass action model where the rate of plasmid growth includes the lag time of newly formed F(+) transconjugants and the recovery time between successive conjugation events of the F(+) donors. By assaying defined mixtures of genotypically identical donor and recipient cells at constant inoculation densities, we extract an F plasmid transfer rate of 5 × 10(-10) (cells/mL · min)(-1). We confirm a plasmid/chromosome ratio of 1:1 in homogenous F(+) populations throughout batch growth. Surprisingly, in some mixture experiments we observe an excess of F plasmid in the early saturation phase that equilibrates to a final ratio of one plasmid per chromosome.