Risk of metastatic disease using [F-18]PSMA-1007 PET/CT for primary prostate cancer staging

Background Accurate prostate cancer imaging is critical for patient management. Multiple studies have demonstrated superior diagnostic accuracy of [Ga-68]-PSMA-11 PET/CT over conventional imaging for disease detection, with validated clinical and biochemical predictors of disease detection. More recently [F-18]PSMA-1007 offers theoretical imaging advantages, but there is limited evidence of clinical and biochemical predictors of scan findings in the staging population. This study investigates the association of clinical variables with imaging characteristics among patients who underwent [F-18]PSMA-1007 PET/CT for primary staging of men with histopathologically confirmed prostate carcinoma. A retrospective review of 194 consecutive patients imaged between May 2019 to May 2020 was performed. Association between imaging variables (presence and distribution of metastatic disease, primary tumour SUVmax) and clinical variables (EAU risk criteria) were assessed using descriptive statistics, logistic regression model and ROC analysis. Results The median age, PSA level and ISUP grade were 70 years, 10 ng/mL and ISUP grade 3, respectively. There were 36.6% of patients with intermediate-risk and 60.8% of patients with high-risk disease. ISUP grade was associated with the presence of metastasis overall (p = 0.008) as well as regional nodal (p = 0.003), non-regional nodal (p = 0.041) and bone (p = 0.006) metastases. PSA level was associated with metastatic disease overall (p = 0.001), regional (p = 0.001) and non-regional nodal metastases (p = 0.004), but not with bone metastases (p = 0.087). There were too few visceral metastases for meaningful analysis. SUVmax of the primary prostatic tumour was associated with ISUP grade (p = 0.004), PSA level (p 20 ng/mL and ISUP grade > 3 had a specificity of 85% (95% CI 78-91%) and 60% (95% CI 50-68%) and a sensitivity of 36% (95% CI 25-49%) and 62% (95% CI 49-74%), respectively, for detection of metastatic disease. Conclusion Metastatic disease according to [F-18]PSMA-1007 PET/CT was associated with ISUP grade and PSA level. This is the largest study using [F-18]PSMA-1007 PET/CT to confirm a positive correlation of PSA level, ISUP grade and stage with primary prostate tumour SUVmax

InnateDB: facilitating systems-level analyses of the mammalian innate immune response

Although considerable progress has been made in dissecting the signaling pathways involved in the innate immune response, it is now apparent that this response can no longer be productively thought of in terms of simple linear pathways. InnateDB (www.innatedb.ca) has been developed to facilitate systems-level analyses that will provide better insight into the complex networks of pathways and interactions that govern the innate immune response. InnateDB is a publicly available, manually curated, integrative biology database of the human and mouse molecules, experimentally verified interactions and pathways involved in innate immunity, along with centralized annotation on the broader human and mouse interactomes. To date, more than 3500 innate immunity-relevant interactions have been contextually annotated through the review of 1000 plus publications. Integrated into InnateDB are novel bioinformatics resources, including network visualization software, pathway analysis, orthologous interaction network construction and the ability to overlay user-supplied gene expression data in an intuitively displayed molecular interaction network and pathway context, which will enable biologists without a computational background to explore their data in a more systems-oriented manner

The Commensal Streptococcus salivarius K12 Downregulates the Innate Immune Responses of Human Epithelial Cells and Promotes Host-Microbe Homeostasis▿ †

Streptococcus salivarius is an early colonizer of human oral and nasopharyngeal epithelia, and strain K12 has reported probiotic effects. An emerging paradigm indicates that commensal bacteria downregulate immune responses through the action on NF-κB signaling pathways, but additional mechanisms underlying probiotic actions are not well understood. Our objective here was to identify host genes specifically targeted by K12 by comparing their responses with responses elicited by pathogens and to determine if S. salivarius modulates epithelial cell immune responses. RNA was extracted from human bronchial epithelial cells (16HBE14O- cells) cocultured with K12 or bacterial pathogens. cDNA was hybridized to a human 21K oligonucleotide-based array. Data were analyzed using ArrayPipe, InnateDB, PANTHER, and oPOSSUM. Interleukin 8 (IL-8) and growth-regulated oncogene alpha (Groα) secretion were determined by enzyme-linked immunosorbent assay. It was demonstrated that S. salivarius K12 specifically altered the expression of 565 host genes, particularly those involved in multiple innate defense pathways, general epithelial cell function and homeostasis, cytoskeletal remodeling, cell development and migration, and signaling pathways. It inhibited baseline IL-8 secretion and IL-8 responses to LL-37, Pseudomonas aeruginosa, and flagellin in epithelial cells and attenuated Groα secretion in response to flagellin. Immunosuppression was coincident with the inhibition of activation of the NF-κB pathway. Thus, the commensal and probiotic behaviors of S. salivarius K12 are proposed to be due to the organism (i) eliciting no proinflammatory response, (ii) stimulating an anti-inflammatory response, and (iii) modulating genes associated with adhesion to the epithelial layer and homeostasis. S. salivarius K12 might thereby ensure that it is tolerated by the host and maintained on the epithelial surface while actively protecting the host from inflammation and apoptosis induced by pathogens