Search

The murine maternal immune activation (MIA) offspring model enables longitudinal studies to explore aberrant social behaviors similar to those observed in humans. High levels of cytokines, chemokines and cell adhesion molecules (CAM) have been found in the plasma and/or brains of psychiatric patients. We hypothesized that upregulation of the systemic or brain immune response has an augmenting effect by potentially increasing the interplay between the neuronal and immune systems during the growth of the MIA offspring. In this study, a C57BL/6j MIA female offspring model exhibiting social deficits was established. The expression of fetal interferon (IFN)‐stimulated (gbp3, irgm1, ifi44), adolescent immunodevelopmental transcription factor (eg, r2, tfap2b), hormone (pomc, hcrt), adult selectin (sell, selp) and neuroligin (nlgn2) genes was altered. Systemic upregulation of endogenous IL‐10 occurred at the adult stage, while both IL‐1β and IL‐6 were increased and persisted in the sera throughout the growth of the MIA offspring. The cerebral IL‐6 levels were endogenously upregulated, but both MCP‐1 (macrophage inflammatory protein‐1) and L‐selectin levels were downregulated at the adolescent and/or adult stages. However, the MIA offspring were susceptible to lipopolysaccharide (LPS) stimulation. After reinjecting the MIA offspring with LPS in adulthood, a variety of sera and cerebral cytokines, chemokines and CAMs were increased. Particularly, both MCP‐1 and L‐selectin showed relatively high expression in the brain compared with the expression levels in phosphate‐buffered saline (PBS)‐treated offspring injected with LPS. Potentially, MCP‐1 was attracted to the L‐selectin‐mediated immune cells due to augmentation of the immune response following stimulation in MIA female offspring. [ABSTRACT FROM AUTHOR]

Macrophages express a broad range of plasma membrane receptors that mediate their interactions with natural and altered-self components of the host as well as a range of microorganisms. Recognition is followed by surface changes, uptake, signaling, and altered gene expression, contributing to homeostasis, host defense, innate effector mechanisms, and the induction of acquired immunity. This review covers recent studies of selected families of structurally defined molecules, studies that have improved understanding of ligand discrimination in the absence of opsonins and differential responses by macrophages and related myeloid cells. [ABSTRACT FROM AUTHOR]

Background: Data mining from a published transcriptome of urinary bladder urothelial carcinomas (GSE32894), PTP4A3 was identified as the most significantly upregulated gene among those related to prenylated protein tyrosine phosphatase activity (GO: 0004727). We therefore analysed PTP4A3 transcript and protein expression and their clinicopathological and prognostic significance in our well-characterised cohort of urothelial carcinomas. Methods: PTP4A3 transcript level was assessed in 23 samples of urothelial carcinoma of the urinary bladder with laser capture microdissection coupled with real-time qRT-PCR. PTP4A3 protein expression was determined by immunohistochemistry and evaluated by using H-score in 296 urinary bladder urothelial carcinomas and 340 upper urinary tract urothelial carcinomas, respectively. Both transcript and protein expression statuses were further correlated with clinicopathological features and protein expression was tested for disease-specific survival (DSS) and metastasis-free survival (MeFS). Findings: PTP4A3 transcripts were markedly upregulated in deeply invasive urothelial carcinomas (p<0.001). For both urinary tract and urinary bladder urothelial carcinomas, PTP4A3 protein overexpression was significantly associated with advanced pT status (both p<0.001), nodal metastasis (both p<0.001), and vascular invasion (both p<0.001). PTP4A3 overexpression not only predicted worse DSS (both p<0.0001) and MeFS (upper urinary tract, p<0.0001; urinary bladder, p=0.0005) at univariate analysis, but also inferior DSS (upper urinary tract, p=0.001; urinary bladder, p<0.001) and MeFS (upper urinary tract, p=0.001; urinary bladder, p=0.007) in multivariate analysis. Interpretation: PTP4A3 overexpression is an independent prognosticator for urothelial carcinoma, suggesting its potential prognostic and therapeutic value in urothelial carcinoma. [ABSTRACT FROM AUTHOR]

Background: Through data mining from a published transcriptomic database of urinary bladder urothelial carcinomas (GSE32894), MMP11 was identified as the most significant gene showing stepwise upregulation among those associated with the regulation of metalloendopeptidase activity. We therefore analysed MMP11 protein expression and its association with clinicopathological factors and survival in our well-characterised cohort of urothelial cancers. Methods: Immunohistochemistry evaluated by using H-score was used to determine MMP11 protein expression in 295 urothelial carcinomas of the urinary bladder and 340 urothelial carcinomas of the upper urinary tract, respectively. The medical records of these patients were reviewed retrospectively. The MMP11 expression status was further correlated with clinicopathological features as well as disease-specific survival (DSS) and metastasis-free survival (MeFS). Univariate and multivariate statistical analyses were performed to evaluate the prognostic predictors. Findings: MMP11 protein overexpression was significantly associated with advanced pT status (upper urinary tract, p< 0.001; urinary bladder, p<0.001), nodal metastasis (upper urinary tract, p<0.001; urinary bladder, p=0.012), vascular invasion (upper urinary tract, p<0.001; urinary bladder, p<0.001), and perineural invasion (upper urinary tract, p=0.002; urinary bladder, p=0.006) in both groups of urothelial carcinomas. MMP11 overexpression not only predicted worse DSS (upper urinary tract, p<0.0001; urinary bladder, p<0.0001) and MeFS (upper urinary tract, p<0.0001; urinary bladder, p<0.0001) at univariate analysis, but also inferior DSS (upper urinary tract, p=0.005; urinary bladder, p=0.010) and MeFS (upper urinary tract, p=0.018; urinary bladder, p=0.026) in multivariate analysis. Interpretation: MMP11 overexpression is associated with more aggressive tumour phenotype and poor prognosis for patients with urothelial carcinomas of the upper urinary tract and urinary bladder, suggesting it may serve as a potential prognostic and a novel therapeutic target of urothelial carcinoma. [ABSTRACT FROM AUTHOR]

Background: Dipeptidyl peptidase-4 (DPP4), also known as CD26, is an enzyme that cleaves a diversity of protein that contains proline or analine, including chemokines, growth factors, and neuropeptide. Different DPP4 expression status has been observed in malignant tumours, including colon, renal, and ovarian carcinoma. Data mining of the published dataset (GSE31684) identified that DPP4 is significantly upregulated in urothelial carcinoma of the urinary bladder. We therefore analysed the association of DPP4 expression and outcome in our well-characterised cohort of urothelial carcinoma. Methods: Laser capture microdissection coupled with real-time qRT-PCR was used to evaluate DPP4 transcript level in 20 urothelial carcinomas of the urinary bladder. DPP4 immunostaining was done on 340 cases of urothelial carcinoma of the upper urinary tract and 295 cases of urothelial carcinoma of the urinary bladder. The expression status of DPP4 was then correlated with various clincopathological factors, disease-specific survival (DSS), and metastasis-free survival (MeFS). Findings: DPP4 mRNA expression was significantly increased in urothelial carcinomas with higher pT status (p<0.001). In both groups of urothelial carcinomas, increment of DPP4 immunoexpression was significantly associated with advanced pT stage (both p<0.001), high histological grade (urothelial carcinoma of the upper urinary tract, p=0.019), lymph node metastasis (urothelial carcinoma of the upper urinary tract, p<0.001; urothelial carcinoma of the urinary bladder, p=0.033), vascular invasion (both p<0.001), perineurial invasion (urothelial carcinoma of the urinary bladder, p=0.021) and frequent mitosis (urothelial carcinoma of the upper urinary tract, p=0.003). DPP4 overexpression independently predicted poor DSS (urothelial carcinoma of the upper urinary tract, p=0.028; urothelial carcinoma of the urinary bladder, p<0.0001) and MeFS (urothelial carcinoma of the upper urinary tract, p=0.031; urothelial carcinoma of the urinary bladder, p<0.0001) in both groups of patients. Interpretation: Our study shows that overexpression of DPP4 is significantly associated with aggressive tumour behaviour and poor outcome. DPP4 may have an important role in tumorigenesis of urothelial carcinoma. [ABSTRACT FROM AUTHOR]