Recently, gene-based cytokine treatment has been actively pursued as a new promising approach in treating cancer. In an effort to augment the efficiency of antitumor effect by cytokine-mediated immunotherapy, we selected both interleukin (IL)-12 and 4-1BB ligand (4-1BBL) as suitable cytokines to fully activate the type-1 immune response. Coexpression of IL-12 and 4-1BBL mediated by oncolytic adenovirus (Ad) greatly enhanced the antitumor effect. Further, synergistic enhancement in interferon (IFN)-γ levels were seen in mice treated with oncolytic Ad expressing both IL-12 and 4-1BBL. Next, to improve the overall antitumor immune response, we coadministered IL-12- and 4-1BBL-coexpressing oncolytic Ad with dendritic cells (DCs). Combination treatment of IL-12- and 4-1BBL-coexpressing oncolytic Ad and DCs elicited greater antitumor and antimetastatic effects than either treatment alone. Moreover, enhanced type-1 antitumor immune response and higher migratory abilities of DCs in tumors were also observed in the combination arms. The nature of the enhanced antitumor immune response seems to be mediated through the enhanced cytolytic activity of cytotoxic T lymphocytes (CTLs) and IFN-γ-releasing immune cells. Taken together, these data highlight the potential therapeutic benefit of combining IL-12- and 4-1BBL-coexpressing oncolytic Ad with DCs and warrants further evaluation in the clinic.

The objective of this retrospective study is to assess neutrophil to lymphocyte ratio (NLR) and platelet to lymphocyte ratio (PLR) as inflammatory markers in patients with psoriasis and psoriatic arthritis (PsA). A hundred and eleven psoriasis patients and 25 PsA patients were compared with 94 healthy controls. Demographic, clinical and laboratory information were collected and analyzed. NLR and PLR were calculated. White blood cell (WBC), neutrophils, eosinophils and NLR were increased in psoriasis patients compared with controls. WBC, neutrophils, NLR, monocytes, platelets and PLR were increased in PsA patients compared with both controls and psoriasis patients. Erythrocyte sedimentation rate (ESR) and C-reactive protein were significantly higher in PsA patients compared with psoriasis patients. Among psoriasis patients, Psoriasis Area and Severity Index (PASI) score correlated positively with platelets, NLR and PLR. These parameters were all significantly higher in moderate to severe psoriasis patients (PASI ≥ 10) compared with mild patients (PASI < 10). Elevated platelets, NLR and PLR were significantly associated with the increased PASI scores in multivariate analysis. NLR, PLR and ESR were statistically significant predictors for the presence of PsA in psoriasis patients. NLR was the strongest predictor (odds ratio = 3.351, P = 0.005). In conclusion, elevated NLR and PLR were significantly associated with psoriasis and PsA. Both NLR and PLR were strong predictors for the presence of PsA among psoriasis patients.

Oxidative stress results from a prooxidant-antioxidant imbalance, leading to cellular damage. It is mediated by free radicals, such as reactive oxygen species or reactive nitrogen species, that are generated during physiological aerobic metabolism and pathological inflammatory processes. Skin serves as a protective organ that plays an important role in defending both external and internal toxic stimuli and maintaining homeostasis. It is becoming increasingly evident that oxidative stress is involved in numerous skin diseases and that antioxidative strategies can serve as effective and easy methods for improving these conditions. Herein, we review dysregulated antioxidant systems and antioxidative therapeutic strategies in dermatology.

PLINK: a tool set for whole-genome association and population-based linkage analyses.

PurposeThis retrospective study was done to investigate the mean platelet volume (MPV) level in patients with psoriasis vulgaris and its relationship with disease severity.Materials and MethodsWe undertook a cross-sectional study on 176 patients and 101 healthy controls to examine the association between MPV and psoriasis. Various clinical and laboratory parameters were analyzed and compared.ResultsPlatelet distribution width and MPV were significantly higher in patients with psoriasis than controls. In addition, there was positive correlation between Psoriasis Area Severity Index (PASI) and MPV. When psoriasis patients were grouped into mild psoriasis (PASI<10) and moderate to severe psoriasis (PASI≥10), the MPV of the latter group was significantly elevated. Nevertheless, patients with higher MPV level (MPV≥10.4 fL) did not show higher PASI than lower MPV level (MPV<10.4 fL). MPV levels significantly decreased after improvements of psoriasis with various treatments. The variations of MPV and PASI also showed significant correlation.ConclusionWe have shown that MPV is increased in psoriasis patients and correlates with disease severity. Therefore, MPV levels may be considered as a marker of disease severity of psoriasis.

Background There has been little research on extramammary Paget's disease (EMPD)

Perivasculitis and endothelial cell abnormalities are prominent histopathologic features of syphilis. Various cutaneous lesions are the main clinical features of syphilis. We examined whether Treponema pallidum 47 kDa antigen regulates the expression of cell adhesion molecules on human dermal microvascular endothelial cells (HDMEC) and the regulation of T-lymphocytes binding to HDMEC. Using immunofluorescence flow cytometry and enzyme-linked immunosorbent assay (ELISA), we demonstrated that T. pallidum upregulated the expression of adhesion molecules, including intercellular adhesion molecule 1 (ICAM-1), vascular cell adhesion molecule 1 (VCAM-1) and E-selectin. The 47 kDa antigen of T. pallidum also activated endothelium as measured by the upregulation of the expression of adhesion molecules on HDMEC, and it also promoted an increased adherence of T-lymphocytes to HDMEC. The expressions of ICAM-1 and VCAM-1 on HDMEC and the adherence of T-lymphocytes to HDMEC were inhibited by treatment with anti-TNF-alpha antibody or anti-IL-1alpha antibody. These results show that T. pallidum or T. pallidum-specific 47 kDa antigen are capable of stimulating HDMEC to increase the expression of ICAM-1, VCAM-1 and E-selectin and thereby, promote the adherence of T-lymphocytes. The whole process may play an important role in the immunopathogenesis of syphilis and it is likely that TNF-alpha and IL-1alpha are involved.

Psoriasis is a chronic inflammatory skin disease that is thought to be related to oxidative stress. Much progress has been made in understanding the pathophysiology of psoriasis in relation to the immunologic and antioxidant systems. However, this progress has been hindered by the lack of an appropriate animal model for psoriasis. Recently, imiquimod (IQM)-induced psoriasis-like cutaneous inflammation has been reported in mice and humans. We verified the usefulness of an IQM-induced mouse model in relation to the antioxidant system. BALB/C female mice at 8-10 weeks of age were treated with IQM cream in this study. We analyzed clinical and histopathological changes. Increased reactive oxygen species production was measured by glutathione assay. Levels of myeloperoxidase (MPO) and superoxide dismutase-1 (SOD1) were determined by western blotting and immunohistochemical analyses. The activity of SOD was measured by a SOD activity assay kit. Application of IQM-induced skin inflammation similar to psoriasis in clinical and histopathological aspects. Accumulation of immune cells was confirmed. Oxidative stress was increased, the antioxidant enzyme MPO levels were increased, and both SOD levels and activity were decreased. In conclusion, the IQM-induced mouse model showed an aberrant antioxidant system. Levels of MPO and oxidative stress were increased, and the level and activity of SOD were decreased. Since this model seemed to be an appropriate model for psoriasis, it can be used to further study the pathogenic role of redox imbalance in psoriasis.