No abstract

ABSTRACTThe consumption of raw oysters is an important risk factor in the acquisition of food-borne disease, withSalmonellabeing one of a number of pathogens that have been found in market oysters. Previous work by our lab found thatSalmonellawas capable of surviving in oysters for over 2 months under laboratory conditions, and this study sought to further investigateSalmonella's tissue affinity and mechanism of persistence within the oysters. Immunohistochemistry was used to show thatSalmonellawas capable of breaching the epithelial barriers, infecting the deeper connective tissues of the oysters, and evading destruction by the oysters' phagocytic hemocytes. To further investigate the mechanism of these infections, genes vital to the function ofSalmonella's two main type III secretion systems were disrupted and the survivability of these knockout mutants within oysters was assayed. When theSalmonellapathogenicity island 1 and 2 mutant strains were exposed to oysters, there were no detectable deficiencies in their abilities to survive, suggesting thatSalmonella's long-term infection of oysters does not rely upon these two important pathogenicity islands and must be due to some other, currently unknown, mechanism.

ObjectiveTo evaluate the role of concurrent systemic therapy to postoperative radiation therapy (RT) for locally advanced cutaneous head and neck squamous cell carcinoma (LA-cHNSCC).Materials and methodsA retrospective study of 32 patients with LA-cHNSCC receiving postoperative RT with and without systemic therapy was conducted. Patients with LA-cHNSCC after surgical resection with one or more high risk features were evaluated. Local regional control (LRC), distant control (DC), and acute and late toxicities were evaluated with Fisher exact tests. Progression-free survival (PFS) and overall survival (OS) were evaluated utilizing Kaplan Meier and log-rank analyses. Univariate Cox proportional hazard analyses were used to examine patient, disease, and treatment-related factors with OS and PFS.ResultsWhile comparing patients receiving RT with systemic therapy (n = 14) vs RT alone (n = 18), LRC was 92.9% vs 72.2% (p = 0.20), DC 92.9% vs 94.4% (p = 1.0), median PFS 17.7 months vs 34.4 months (p = 0.48), and median OS 20.9 months vs 34.4 months (p = 0.03), respectively. On univariate analyses, use of concurrent systemic therapy was associated with an increased risk of death with an HR of 3.5 [95% confidence interval (CI): 1.04 - 11.6] (p = 0.04), while patients treated for recurrent disease who had previously treated superficial primaries had improved OS with an HR of 0.10 [95% CI: 0.01-0.80] (p = 0.03). There were no significant differences in acute or chronic toxicities between groups.ConclusionsPatients receiving postoperative RT alone for LA-cHNSCC had better OS than patients receiving concurrent systemic therapy. There were no differences in any other endpoints evaluated.

Treatment failures of glioblastoma (GBM) occur within high-dose radiation fields. We hypothesized that this is due to increased capacity for DNA damage repair in GBM. We identified 24 adult GBM patients treated with maximal safe resection followed by radiation with concurrent and adjuvant temozolomide. The mRNA from patients was quantified using NanoString Technologies’ nCounter platform and compared with 12 non-neoplastic temporal lobe tissue samples as a control. Differential expression analysis identified seven DNA repair genes significantly upregulated in GBM tissues relative to controls (>4-fold difference, adjusted p values < 0.001). Among these seven genes, Cox proportional hazards models identified RAD51 to be associated with an increased risk of death (HR = 3.49; p = 0.03). Kaplan–Meier (KM) analysis showed that patients with high RAD51 expression had significantly shorter OS compared to low levels (median OS of 10.6 mo. vs 20.1 mo.; log-rank p = 0.03). Our findings were validated in a larger external dataset of 162 patients using publicly available gene expression data quantified by the same NanoString technology (median OS of 13.8 mo. vs. 17.4 mo; log-rank p = 0.006). Within this uniformly treated GBM population, RAD51, in the homologous recombination pathway, was overexpressed (vs. normal brain) and inversely correlated with OS. High RAD51 expression may be a prognostic biomarker and a therapeutic target in GBM.

mutations by DNA-based NGS, including 12 (80%) cases with splice donor site mutations, 1 (6.67%) cases with splice acceptor site alterations, 1 (6.67%) case with a novel deletion (chr7: 116411868 -116411883) at MET intron 13 region and 1 (6.67%) case with a novel deletion (chr7: 116412027 -116412042) at MET exon14 region. In this study, 6 somatic mutations which induce METex14 skipping were firstly discovered. So far, RT-PCR and Sanger sequencing were performed on 3 specimens, including 1 sample with conflicting RNA-and DNA-based NGS results and 2 samples with unreported somatic deletions. According to the results of RT-PCR and Sanger, the unmatched sample was false negative on the basis of DNA-based NGS result. Interestingly, METex14 skipping was mutually exclusive with other recognized genomic alterations (such as mutations in KRAS, BRAF, EGFR, NRAS and PIK3CA), while no significant difference was found between METex14 skipping and single driver gene. Conclusion: Mutational events of MET leading to exon 14 skipping are frequent occurred in Chinese PSC patients. DNA-based NGS could discover new somatic mutations which results in METex14 skipping. However, RNAbased NGS could provide more accurate results than DNA-based NGS. METex14 skipping was mutually exclusive with other drivers, thus strongly highlighting its potential oncogenic role.