The prognostic role of tertiary Gleason pattern 5 in a contemporary grading system for prostate cancer.

BACKGROUND: Recently, a new prostate cancer (PC) grading system has been introduced, where Gleason score (GS) 7 (3+4) and GS 7 (4+3) are categorized into two separate groups. However, GS 7 with tertiary Gleason pattern 5 (TGP5) was not incorporated in the new grading system. In the present study, we validated the prognostic role of TGP5 in the new classification. METHODS: We retrospectively reviewed the records of 1396 patients with localized GS 6-8 PC (pT2-3N0M0) who underwent radical prostatectomy at our institution between 2005 and 2014. After excluding patients who received neoadjuvant or adjuvant therapy, or had incomplete pathological or follow-up data, 1229 patients were included in the final analysis. The Kaplan-Meier method was used to estimate and compare the probabilities of biochemical recurrence (BCR). Cox regression models were used to investigate associations between variables and the risk of BCR. RESULTS: Of 732 GS 7 patients, 75 (10.2%) had a TGP5. The BCR-free survival rate for men with TGP5 was significantly worse than for those without TGP5 (P<0.001). In multivariate Cox regression analyses for GS 7 PC, TGP5 was a significant predictor of BCR (hazard ratio 1.750, P=0.027). When the total cohort was stratified into four grade groups according to the new classification, group 2 with TGP5 had a BCR risk comparable to group 3, and group 3 with TGP5 behaved like group 4. CONCLUSIONS: Our study shows that TGP5 increased the BCR risk after RP in GS 7 PC. Moreover, we demonstrated that the presence of a TGP5 in GS 7 upgraded the BCR risk to one comparable with the next higher category under the new classification. These findings support incorporating TGP5 into GS 7 to aid with future risk assessment and follow-up scheduling for PC.

Prognostic impact of preoperative neutrophil-to-lymphocyte ratio after radical prostatectomy in localized prostate cancer.

BACKGROUND: Neutrophil-to-lymphocyte ratio (NLR) has a prognostic value in patients with metastatic castration-resistant prostate cancer receiving systemic therapy. However, the prognostic significance of NLR was never previously evaluated in patients who underwent radical prostatectomy (RP) for prostate cancer. In the present study, we investigated the influence of NLR on survival after a RP for prostate cancer. METHODS: We retrospectively reviewed clinical data of 2301 patients with prostate cancer who underwent RP at our institution between 2000 and 2010. Among these patients, we considered only patients who had a preoperative complete blood count with differential result available. Patients who received neoadjuvant or postoperative adjuvant treatment (radiation, androgen deprivation therapy or both) and those without adequate medical record were excluded. A Kaplan-Meier analysis was performed to analyze biochemical recurrence-free survival (BCRFS), overall survival (OS) and prostate cancer-specific survival (CSS). Univariate and multivariate Cox regression models were used for each end point. RESULTS: In total, 2067 patients were evaluated; median follow-up time was 78 months (interquartile range (IQR) 65-96), median age at RP was 66 years (IQR 61-70) and median preoperative NLR was 1.76 (IQR 1.35-2.40). A Kaplan-Meier analysis showed a significant association between high NLR (⩾1.76) and decreased CSS (P=0.005) and OS (P=0.003) but not with BCRFS (P=0.223). In the univariate and multivariate regression analyses, a high NLR was a significant predictor of CSS (hazard ratio (HR) 2.012, 95% confidence interval (CI) 1.222-3.310, P=0.006) and OS (HR 1.650, 95% CI 1.127-2.416, P=0.010). CONCLUSIONS: This study shows that in patients with prostate cancer preoperative NLR is an independent prognostic factor for OS and CSS after a RP and suggests that a preoperative hematologic workup should be considered in the risk assessment of these patients.

Suppression of PPARγ through MKRN1-mediated ubiquitination and degradation prevents adipocyte differentiation.

The central regulator of adipogenesis, PPARγ, is a nuclear receptor that is linked to obesity and metabolic diseases. Here we report that MKRN1 is an E3 ligase of PPARγ that induces its ubiquitination, followed by proteasome-dependent degradation. Furthermore, we identified two lysine sites at 184 and 185 that appear to be targeted for ubiquitination by MKRN1. Stable overexpression of MKRN1 reduced PPARγ protein levels and suppressed adipocyte differentiation in 3T3-L1 and C3H10T1/2 cells. In contrast, MKRN1 depletion stimulated adipocyte differentiation in these cells. Finally, MKRN1 knockout MEFs showed an increased capacity for adipocyte differentiation compared with wild-type MEFs, with a concomitant increase of PPARγ and adipogenic markers. Together, these data indicate that MKRN1 is an elusive PPARγ E3 ligase that targets PPARγ for proteasomal degradation by ubiquitin-dependent pathways, and further depict MKRN1 as a novel target for diseases involving PPARγ.

An epidemiological study of androgenic alopecia in 3114 Korean patients.

BACKGROUND: Androgenetic alopecia (AGA) is the most common type of hair loss, and is characterized by the transformation of terminal scalp hair into vellus hair. The epidemiology of AGA is not fully understood. A strong genetic basis has long been identified, although little is known of its nongenetic causes. AIM: To evaluate the association of AGA with a number of environmental factors, including smoking, drinking and sleeping habit. METHODS: In total, 3114 Korean individuals with AGA who attended any one of 17 dermatology clinics in 6 cities in South Korea between March 2011 and February 2012 were enrolled in the study. Epidemiologic a data were collected using a standard questionnaire. RESULTS: No association was seen between eating or sleeping habits and severity of hair loss. However, drinking and smoking were associated with the severity of AGA in male patients. We also found that patients of both genders with a family history had more advanced types of hair loss, and the age of onset of AGA in male patients with a family history was earlier than that in male patients without a family history. CONCLUSIONS: Although the evidence for an environmental influence on AGA remains very weak, we did find an association between hair loss severity and certain environmental factors, such as smoking and drinking. Family history with more severe hair loss and an earlier age of onset.

Electrophysiological study for comparing the effect of biological activity between type A botulinum toxins in rat gastrocnemius muscle.

BACKGROUND: New cosmetic applications and products based on the effects of botulinum toxin (BTX) treatment have stimulated demand for this class of natural compounds. This demand generates the need for appropriate standardized protocols to test and compare the effectiveness of new BTX preparations. OBJECTIVES: Based on the previously described electrophysiological methods, we measured and compared the inhibitory effects of two BTX type A (BTX-A) preparations on neuromuscular transmission through split-body test. METHODS: The effectiveness was evaluated in terms of the compound muscle action potential (CMAP) and conduction velocity after BTX-A injection. We used a split-body method to compare two different BTX-As in the rat. RESULTS: Based on the changes in the CMAP, the two different BTX-As induced paralytic effect on the rat tibialis anterior muscle. However, the two different BTX-A preparations did not differ significantly in effectiveness and did not induce a delay in conduction velocity. CONCLUSIONS: The new BTX-A preparation used in this electrophysiological study had similar effect compared with the previously marketed BTX-A.[AQ: Please approve the edits made to the sentence "The new BTX-A preparation…") We propose that a split-body electrophysiological protocol will be useful in establishing the comparative effectiveness of new BTX products.

A pilot study of silver-loaded cellulose fabric with incorporated seaweed for the treatment of atopic dermatitis.

Because clothing has the longest and most direct contact with human skin, it is important to carefully choose suitable fabrics for atopic patients who have disrupted skin. To evaluate the clinical effectiveness and biophysical properties of a newly developed silver-loaded cellulose fabric with incorporated seaweed, we enrolled 12 subjects with mild to moderate atopic dermatitis into a clinical control study. The subjects wore a two-piece garment (top and leggings), each piece of which was divided into two parts: one side was made of SkinDoctor(®) fabric, and the other of 100% cotton. Treatment efficacy was measured with the modified SCORing Atopic Dermatitis (mSCORAD) index, transepidermal water loss (TEWL) and the patients' subjective impressions. All three of these measures had significantly better scores on the side covered with SkinDoctor. These results suggest that SkinDoctor is a beneficial fabric that can improve the comfort of patients with AD.

New mechanism of oral immunity to mucosal candidiasis in hyper-IgE syndrome.

Oropharyngeal candidiasis (OPC, thrush) is an opportunistic infection caused by the commensal fungus Candida albicans. An understanding of immunity to Candida has recently begun to unfold with the identification of fungal pattern-recognition receptors such as C-type lectin receptors, which trigger protective T-helper (Th)17 responses in the mucosa. Hyper-IgE syndrome (HIES/Job's syndrome) is a rare congenital immunodeficiency characterized by dominant-negative mutations in signal transducer and activator of transcription 3, which is downstream of the Th17-inductive cytokines interleukin (IL)-6 and IL-23, and hence patients with HIES exhibit dramatic Th17 deficits. HIES patients develop oral and mucocutaneous candidiasis, supporting a protective role for Th17 cells in immunity to OPC. However, the Th17-dependent mechanisms of antifungal immunity in OPC are still poorly defined. An often unappreciated aspect of oral immunity is saliva, which is rich in antimicrobial proteins (AMPs) and exerts direct antifungal activity. In this study, we show that HIES patients show significant impairment in salivary AMPs, including ß-defensin 2 and Histatins. This tightly correlates with reduced candidacidal activity of saliva and concomitantly elevated colonization with Candida. Moreover, IL-17 induces histatins in cultured salivary gland cells. This is the first demonstration that HIES is associated with defective salivary activity, and provides a mechanism for the severe susceptibility of these patients to OPC.

Purification, cDNA cloning and expression of an insect defensin from the great wax moth, Galleria mellonella.

An insect defensin, named Galleria defensin, was purified from the larval haemolymph of Galleria mellonella immunized against E. coli. The peptide was composed of forty-three amino acid residues containing six cysteines that might be engaged in intramolecular disulphide bridges. The primary structure of Galleria defensin shared about 90.7% identity to that of heliomicin, which was an insect defensin isolated from Heliothis virescens. The full-length cDNA encoding Galleria defensin was cloned from the fat body of the immunized G. mellonella larvae. Northern blot analysis revealed that Galleria defensin was expressed not only in the fat body but also in the midgut against invading bacteria into haemocoel. This is the first report presenting cDNA and expression of an insect defensin in the lepidopteran species.