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The signal-responsive E3 ubiquitin ligase pellino 1 (PELI1) regulates TLR and T cell receptor (TCR) signaling and contributes to the maintenance of autoimmunity; however, little is known about the consequence of mutations that result in upregulation of PELI1. Here, we developed transgenic mice that constitutively express human PELI1 and determined that these mice have a shorter lifespan due to tumor formation. Constitutive expression of PELI1 resulted in ligand-independent hyperactivation of B cells and facilitated the development of a wide range of lymphoid tumors, with prominent B cell infiltration observed across multiple organs. PELI1 directly interacted with the oncoprotein B cell chronic lymphocytic leukemia (BCL6) and induced lysine 63-mediated BCL6 polyubiquitination. In samples from patients with diffuse large B cell lymphomas (DLBCLs), PELI1 expression levels positively correlated with BCL6 expression, and PELI1 overexpression was closely associated with poor prognosis in DLBCLs. Together, these results suggest that increased PELI1 expression and subsequent induction of BCL6 promotes lymphomagenesis and that this pathway may be a potential target for therapeutic strategies to treat B cell lymphomas. [ABSTRACT FROM AUTHOR]

The article presents a case study of a fourteen-year-old boy who was admitted due to chronic recurrent vomiting and abdominal discomfort. Symptoms began several months previously and intensified to occurrence of vomiting once in a day. It is noted that there was no remarkable family history aside from hyperthyroidism in his farther. Initially, prednisolone therapy was administered to the patient.

Background. Although most patients with classical Hodgkin's lymphoma (cHL) have a long survival duration, the current risk stratification is imperfect. A recent study suggested a prognostic role for the peripheral blood absolute lymphocyte count/absolute monocyte count (ALC/AMC) ratio at diagnosis in cHL. It is intriguing to investigate the significance of the ALC/AMC ratio in relation to tumor-associated macrophages (TAMs), yet another prognostic factor for cHL. Methods. We examined the prognostic impact of the ALC, AMC, and ALC/AMC ratio in 312 cHL patients (median age, 37 years) using receiver operating characteristic curve analysis for optimal cutoff values, and compared these with TAM content. Results. The median follow-up was 65 months (range, 0.1--245 months). On univariate analysis, a low ALC/AMC ratio (<2.9) was correlated with a poorer overall survival (OS) outcome. A subgroup analysis of patients with limited- stage disease showed that the ALC/AMC ratio was significantly correlated with the OS time. Multivariate analysis showed the ALC/AMC ratio to be an independent prognostic factor for OS outcome. A Spearman correlation test of TAM content showed a negative correlation with the ALC/AMC ratio and a positive correlation with the peripheral blood macrophage percentage. Conclusions. This study suggests that the ALC/AMC ratio may be a simple, inexpensive, and independent prognostic factor for OS outcome in patients with cHL and may have a role in the stratification of cHL patients in addition to the International Prognostic Score and TAM content. [ABSTRACT FROM AUTHOR]

Idiopathic pulmonary fibrosis is a fatal disease characterized by progressive destruction of the lung. Although TLR2 bridges innate and adaptive immunity by sensing tissue damage, its role in pulmonary fibrosis remains unclear. To address this issue, TLR2-/- and WT mice were examined for bleomycin-induced pulmonary fibrosis (BIPF). Flow cytometric and immunohistochemical analysis revealed that TLR2 expression in bronchial epithelial and immune cells of the lungs was upregulated in WT mice during BIPF. Levels of IL-27, TGF-β, chemokines, and hydroxyproline were lower in lungs of TLR2-/- mice than in those of WT mice, but IL-17 levels were higher in TLR2-/- mice. In in vivo experiments using bone marrow-chimeric mice, TLR2 expression on respiratory epithelial cells, rather than immune cells, induced IL-27 and chemokine production in the lungs, further stimulating BIPF. This effect of TLR2 depended on IRF complexes and MyD88. BIPF was more severe in IL-17A-/- mice and in TLR2-/- mice treated with anti-IL-17 mAb than in TLR2-/- and WT mice. Furthermore, IL-27 blockade in WT mice reduced hydroxyproline levels by enhancing IL-17 production, whereas the treatment of TLR2-/- mice with a chemokine mixture increased hydroxyproline levels by recruiting inflammatory cells into the lungs. TLR2 signaling promotes BIPF by inducing IL-27 and chemokine production by respiratory epithelial cells, thereby inhibiting IL-17 production and recruiting inflammatory cells into the lungs. [ABSTRACT FROM AUTHOR]

Background We evaluated the predictive significance of 14 reported markers using immunohistochemical study in nasopharyngeal carcinoma. Methods Immunohistochemical stainings were done in 38 patients for Met, cyclooxygenase-2 (COX-2), nm23-H1, epidermal growth factor receptor (EGFR), p63, early growth response factor 1 (Egr1), chromosome segregation 1-like (CSE1L), cathepsin-D (aspartyl protease), C-erbB2, p53, signal transducers and activators of transcription (STAT3/STAT5), CD138 (Syndecan-1), and LIN28 with the usual methods. Results The median follow-up time was 30 months (11-83 months). High Met and CD138 expression were statistically significant negative prognostic factors on survival. The expression of Egr1 had a positive prognostic effect on survival. The combined score of these 3 markers, Met plus CD138 minus Egr1, was a strong prognostic factor. The median survival curve was distinctly separated in accord with this combined score. No prognostic value was revealed in COX-2, nm23-H1, EGFR, p63, CSE1L, cathepsin-D, C- erbB2, p53, STAT3, STAT5, and LIN28. Conclusions The combined score of these markers could be used to stratify biomolecular risk groups. © 2010 Wiley Periodicals, Inc. Head Neck, 2010 [ABSTRACT FROM AUTHOR]

* Context.--Grade Group assessed using Gleason combined score and tumor extent is a main determinant for risk stratification and therapeutic planning of prostate cancer. Objective.--To develop a 3-dimensional magnetic resonance imaging (MRI) model regarding Grade Group and tumor extent in collaboration with uroradiologists and uropathologists for optimal treatment planning for prostate cancer. Design.--We studied the data from 83 patients with prostate cancer who underwent multiparametric MRI and subsequent MRI--transrectal ultrasound fusion biopsy and radical prostatectomy. A 3-dimensional MRI model was constructed by integrating topographic information of MRI-based segmented lesions, biopsy paths, and histopathologic information of biopsy specimens. The multiparametric MRI--integrated Grade Group and laterality were assessed by using the 3-dimensional MRI model and compared with the radical prostatectomy specimen. Results.--The MRI-defined index tumor was concordant with radical prostatectomy in 94.7% (72 of 76) of cases. The multiparametric MRI--integrated Grade Group revealed the highest agreement (weighted j, 0.545) and a significantly higher concordance rate (57.9%) than the targeted (47.8%, P=.008) and systematic (39.4%, P=.01) biopsies. The multiparametric MRI--integrated Grade Group showed significantly less downgrading rates than the combined biopsy (P = .001), without significant differences in upgrading rate (P = .06). The 3-dimensional multiparametric MRI model estimated tumor laterality in 66.2% (55 of 83) of cases, and contralateral clinically significant cancer was missed in 9.6% (8 of 83) of cases. The tumor length measured by multiparametric MRI best correlated with radical prostatectomy as compared with the biopsy-defined length. Conclusions.--The 3-dimensional model incorporating MRI and MRI--transrectal ultrasound fusion biopsy information easily recognized the spatial distribution of MRIvisible and MRI-nonvisible cancer and provided better Grade Group correlation with radical prostatectomy specimens but still requires validation. [ABSTRACT FROM AUTHOR]