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Background Marital status has been reported as an independent prognostic factor in various types of malignancies. However, the association between marital status and outcomes of patients with adenocarcinoma of the esophagogastric junction (AEG) has not been fully explored. To this end, we aimed to investigate the effect of marital status on survival of AGE patients. Methods The Surveillance Epidemiology and End Results (SEER) database (2010–2015) was used to extract eligible patients with Siewert type II AEG. Meanwhile, propensity score matching was performed to match 1576 unmarried patients with 1576 married patients. Kaplan–Meier method with log-rank test was used to plot survival curves, univariate and multivariate Cox regression analyses were adopted to investigate the association of marital status with overall survival (OS) and cancer-specific survival (CSS) in AEG patients before and after matching. Results Multivariate analysis in the unmatched cohort revealed that marital status was an independent prognostic factor in patients with Siewert type II AEG. Unmarried patients had poorer OS (hazard ratio [HR]: 1.22, 95% confidence interval [CI]: 1.12–1.29, P < .001) and poorer CSS (HR: 1.19, 95% CI: 1.10–1.29, P < .001) than married patients before matching. Additionally, widowed patients had the poorest OS (HR: 1.26, 95% CI: 1.11–1.44, P < .001) and CSS (HR: 1.29, 95% CI: 1.12–1.48, P < .001) compared with married patients. Furthermore, unmarried status remained as an independent prognostic for both OS (HR: 1.20, 95% CI: 1.10–1.31, P < .001) and CSS (HR: 1.18, 95% CI: 1.08–1.30, P < .001) in 1:1 propensity score-matched analysis. Subgroup analysis further revealed that OS and CSS rates were significantly higher in married patients than unmarried ones in most subgroups stratified by different variables. Conclusions This population-based study identified that marital status was an independent prognostic indicator for AEG patients. Married AEG patients had better prognosis than their unmarried counterparts.

Background Whether a sequential or concurrent regimen of anthracyclines and taxanes is superior for breast cancer is controversial. We compared the efficacy of two regimens in patients with operable breast cancer based on all relevant published data of phase III randomized controlled trials. Methods A comprehensive literature search on PubMed, Web of Science, Embase, ScienceDirect, Google Scholar, and ClinicalTrials.gov databases was performed up to May 2020. Meta-analysis was performed to evaluate the different efficacy on disease-free survival (DFS) and overall survival (OS) for the two chemotherapy regimens. Subgroup analyses were further carried out in terms of node status and anthracycline selection. Results Compared to the concurrent regimen, the sequential regimen did not improve the DFS or OS in the population studied. Subgroup analysis showed that in node-positive patients, the sequential regimen had better DFS, but not OS, than the concurrent regimen. In sequential regimen, patients who received doxorubicin and taxanes had improved DFS and OS than patients who were administered epirubicin and taxanes. Furthermore, for patients who received doxorubicin and taxanes, compared to the sequential regimen, fewer cycles (4 cycles) of concurrent treatment resulted in a worse DFS and OS, which can be rescued by more cycles (6 cycles). Conclusions The sequential regimen of anthracyclines and taxanes for patients with operable breast cancer did not yield a significant benefit in DFS or OS over the concurrent regimen. The sequential regimen, however, provided a better DFS than concurrent regimen for node-positive patients. Interestingly, further subgroup analysis showed that for node-positive patients who were given doxorubicin and taxanes, more cycles (6 cycles) of the concurrent regimen may rescue the efficacy for fewer cycles (4 cycles).

Epstein-Barr virus (EBV)-associated nasopharyngeal carcinoma (NPC) is one of the most common head and neck malignancies in southern China and Southeast Asia. Unfortunately, 70% of NPC patients have locally advanced disease at the first diagnosis. Radiotherapy alone and concurrent chemoradiotherapy are important treatment approaches for NPC, but they have a limited effect on patients with locally advanced or distantly metastatic disease. 1-5 Nevertheless, the unique immune environment of the EBV-associated NPC provides rational targets for immunotherapy. Diverse types of immunotherapies are actively being studied, including adoptive immunotherapy, therapeutic vaccines, immune checkpoint inhibitors, lytic-induction therapy, and viral immunotherapy. Specifically, adoptive immunotherapy with lymphocyte infusion was well tolerated and effective in 71.4% of patients combined with first-line chemotherapy. Several therapeutic vaccines and PD-1/PD-L1 pathway checkpoint inhibitors have shown promising clinic outcomes at phase I/II clinical trials. Moreover, EBV-lytic inducing therapy and viral immunotherapy for NPC are also being investigated. In this review, we summarized the current status, advantages, and disadvantages of each immunotherapy for EBV-associated NPC, which may shed light on developing safer and more effective treatment modalities in the future.

Mutations in the human PAX6 gene produce various phenotypes, including aniridia, Peters' anomaly, autosomal dominant keratitis and familial foveal dysplasia. The various phenotypes may arise from different mutations in the same gene. To test this theory, we performed a functional analysis of two missense mutations in the paired domain: the R26G mutation, previously reported in a case of Peters' anomaly, and an unreported I87R mutation, which we identified in a patient with aniridia. While both the R26 and the I87 positions are conserved in the paired boxes of all known PAX genes, X-ray crystallography has shown that only R26 makes contact with DNA. We showed that the R26G mutant failed to bind a subset of paired domain binding sites but, surprisingly, bound other sites and successfully transactivated promoters containing those sites. In contrast, the I87R mutant had lost the ability to bind DNA at all tested sites and failed to transactivate promoters. Our data support the haploid-insufficiency hypothesis of aniridia, and the hypothesis that R26G is a hypomorphic allele.

PAX6 is required for proper development of the eye, central nervous system, and nose. PAX6 has two DNA binding domains, a glycine-rich region that links the two DNA binding domains, and a transactivation domain. There is evidence that the different DNA binding domains of PAX6 have different target genes. However, it is not clear if the two DNA binding domains function independently. We have studied the effect of structural changes in the paired domain on the function of PAX6 mediated through its homeodomain. The R26G and I87R mutations have been reported in different human patients with clinically different phenotypes and are in the N- and the C-terminal halves of the paired domain, respectively. Surprisingly, we found that the I87R mutant protein not only lost the transactivation function but also failed to bind DNA by either of its DNA binding domains. In contrast, the R26G mutant protein lost DNA binding through its paired domain but had greater DNA binding and transactivation than wild-type PAX6 on homeodomain binding sites. Like R26G, the 5a isoform showed higher DNA binding than wild-type PAX6. This study demonstrates that the two subdomains of the paired domain influence the function of the homeodomain differentially and also provides an explanation for the difference in phenotypes associated with these mutations.

PAX6 is a transcription factor with two DNA-binding domains (paired box and homeobox) and a proline-serine-threonine (PST)-rich transactivation domain. PAX6 regulates eye development in animals ranging from jellyfish to Drosophila to humans. Heterozygous mutations in the human PAX6 gene result in various phenotypes, including aniridia, Peter's anomaly, autosomal dominant keratitis, and familial foveal dysplasia. It is believed that the mutated allele of PAX6 produces an inactive protein and aniridia is caused due to genetic haploinsufficiency. However, several truncation mutations have been found to occur in the C-terminal half of PAX6 in patients with Aniridia resulting in mutant proteins that retain the DNA-binding domains but have lost most of the transactivation domain. It is not clear whether such mutants really behave as loss-of-function mutants as predicted by haploinsufficiency. Contrary to this theory, our data showed that these mutants are dominant-negative in transient transfection assays when they are coexpressed with wild-type PAX6. We found that the dominant-negative effects result from the enhanced DNA binding ability of these mutants. Kinetic studies of binding and dissociation revealed that various truncation mutants have 3-5-fold higher affinity to various DNA-binding sites when compared with the wild-type PAX6. These results provide a new insight into the role of mutant PAX6 in causing aniridia.