Structural and functional analysis of human prostatic acid phosphatase

Prostatic acid phosphatase (PAP) is the most abundant phosphatase in human prostate tissue/secretions. It is a clinically important protein for its relevance as a biomarker of prostate carcinoma. Furthermore, it has a potential role in fertilization. We describe here most of the features of PAP including gene regulation, gene/protein structure, functions, its role in tumor progression and evolutionary features. PAP has phosphatase activity and is an extensively studied biomarker of prostate cancer. The major action of PAP is to dephosphorylate macromolecules with the help of catalytic residues (His¹² and Asp²⁵⁸) that are located in the cleft between two domains. This article will be of great interest to all those scientists who are working in the area of prostate pathophysiology.     

Pharmacodynamic analysis of apremilast in Japanese patients with moderate to severe psoriasis: Results from a phase 2b randomized trial

We evaluated the pharmacodynamic effects of apremilast in 69 patients who were included in biomarker subanalyses of a phase 2b study that demonstrated the long‐term safety and efficacy of apremilast in Japanese adults with moderate to severe psoriasis. The association between cytokine levels and Psoriasis Area and Severity Index (PASI) improvement was evaluated using linear regression and Spearman’s rank correlation coefficient analysis. At baseline, median plasma levels of interleukin (IL)‐17A, IL‐17F and IL‐22 were elevated versus reference values for healthy individuals, whereas tumor necrosis factor‐α levels were close to normal. With apremilast 30 mg b.i.d., there were significant associations between percentage change in PASI score and percentage change in IL‐17A, IL‐17F and IL‐22 levels at week 16. Findings demonstrate that the efficacy of apremilast in psoriasis is associated with inhibition of key cytokines involved in the pathology of psoriasis.     

Serum vascular endothelial growth factor receptor 3 as a potential biomarker in psoriasis

To discover novel biomarkers of psoriasis, a target‐specific antibody array screening of serum samples from psoriasis patients was initially performed. The results revealed that vascular endothelial growth factor receptor 3 (VEGFR‐3) was significantly elevated in the sera of psoriasis patients, compared to healthy controls. Next, ELISA validation studies in a larger cohort of psoriasis patients (N = 73) were conducted, which confirmed that serum VEGFR‐3 was indeed significantly increased in patients with psoriasis compared to healthy controls (P < 0.001). Furthermore, receiver operating characteristic curve analysis demonstrated that serum VEGFR‐3 exhibited potential in distinguishing healthy controls from psoriasis patients: area under the curve = 0.85, P < 0.001. In addition, serum levels of VEGFR‐3 were correlated with Psoriasis Area Severity Index scores (R = 0.32, P = 0.008) in psoriasis patients. Interestingly, serum VEGFR‐3 levels were significantly elevated in psoriatic arthritis compared to non‐psoriatic arthritis (P = 0.026). A pilot longitudinal study demonstrated that serum levels of VEGFR‐3 could reflect disease progression in psoriasis. Collectively, serum VEGFR‐3 may have a clinical value in monitoring disease activity of psoriasis.     

Autotrophy as a predominant mode of carbon fixation in anaerobic methane-oxidizing microbial communities

The methane-rich, hydrothermally heated sediments of the Guaymas Basin are inhabited by thermophilic microorganisms, including anaerobic methane-oxidizing archaea (mainly ANME-1) and sulfate-reducing bacteria (e.g., HotSeep-1 cluster). We studied the microbial carbon flow in ANME-1/ HotSeep-1 enrichments in stable-isotope–probing experiments with and without methane. The relative incorporation of ¹³C from either dissolved inorganic carbon or methane into lipids revealed that methane-oxidizing archaea assimilated primarily inorganic carbon. This assimilation is strongly accelerated in the presence of methane. Experiments with simultaneous amendments of both ¹³C-labeled dissolved inorganic carbon and deuterated water provided further insights into production rates of individual lipids derived from members of the methane-oxidizing community as well as their carbon sources used for lipid biosynthesis. In the presence of methane, all prominent lipids carried a dual isotopic signal indicative of their origin from primarily autotrophic microbes. In the absence of methane, archaeal lipid production ceased and bacterial lipid production dropped by 90%; the lipids produced by the residual fraction of the metabolically active bacterial community predominantly carried a heterotrophic signal. Collectively our results strongly suggest that the studied ANME-1 archaea oxidize methane but assimilate inorganic carbon and should thus be classified as methane-oxidizing chemoorganoautotrophs.     

Exhaled Nitric Oxide: A Novel Biomarker of Adverse Respiratory Health Effects in Epidemiological Studies

The sampling of exhaled breath is a noninvasive procedure that can be performed easily in adults, children, and patients with respiratory disease. Several studies have demonstrated increased exhaled nitric oxide in patients with pulmonary disease, including asthma. In addition, exhaled nitric oxide may be an elegant tool for monitoring of environmental health effects of air pollution and the prevalence of atopy in epidemiological surveys. Recent literature about exhaled nitric oxide is presented in this article. Technical, physiological, and behavioral confounding factors of exhaled nitric oxide measurement are outlined.     

Metabolomic Study of Biochemical Changes related to toxicity induced by bupleurotoxin Using LC-MSCoupled with a Pattern Recognition Approach

The purpose of this study was to detect changes in urine of mice and to clarify the toxicity induced by bupleurotoxin (BETX) using liquid chromatography/quadrupole time-of-flight mass spectrometry (LC-Q-TOF-MS). A procedure for urine analysis using pattern recognition was proposed to evaluate the toxicity induced by BETX in male BALB/c mice. BETX at 2.5 mg/kg was administered intraperitoneally (i.p.), and urine samples for the metabolomic study were collected from control and BETX experimental groups. Changes in the concentrations of some urine metabolites were detected exclusively in the experimental group. All results suggested that exposure to BETX might cause a disturbance in fatty acid metabolism and the oxidative stress system. These results may not only clarify the underlying mechanism of diverse intoxication effects of BETX but also provide the guidance in preclinical toxicity screening for new drugs.     

The increasing clinical relevance of human papillomavirus type 16 (HPV-16) infection in oropharyngeal cancer

Human papillomavirus type 16 (HPV-16) has been established beyond doubt as a causative agent in oropharyngeal squamous cell carcinoma (SCC). The incidence of oropharyngeal cancer has risen in recent decades, as has the proportion of patients who have a biologically relevant HPV-16 infection. Combined data from 14 recently published studies (2006-2010) show that 57% of 1316 reported cases of oropharyngeal SCC were HPV-16 positive. They had significantly better prognosis (hazard ratio (HR) for 5-year overall survival range 0.05-0.64), although smoking and higher T stage often appear as confounding factors to this favourable prognostic benefit. HPV-16 therefore has increasing importance as a clinically useful prognostic biomarker, but a benefit in survival has been seen in the use of surgery, radiotherapy, and chemotherapy, so specific changes in the preferred methods of treatment are hard to justify. Future trials that include oropharyngeal SCC will consider HPV-16 routinely as a stratification factor, and its use as a predictive biomarker awaits the development of effective targeted treatments. The undeniable and impressive prognostic significance of HPV-16 should hasten its addition to standard pathological reporting of oropharyngeal SCC, and ultimately to its inclusion in TNM staging systems of the American Joint Committee on Cancer (AJCC) and the International Union against Cancer (UICC).     

Stage-specific prognostic biomarkers in melanoma

The melanoma staging system proposed by the American Joint Committee on Cancer (AJCC) (which classifies melanoma patients into four clinical stages) is currently the most widely used tool for melanoma prognostication, and clinical management decision making by clinicians. However, multiple studies have shown that melanomas within specific AJCC Stages can exhibit varying progression and clinical outcomes. Thus, additional information, such as that provided by biomarkers is needed to assist in identifying the patients at risk of disease progression.Having previously found six independent prognostic biomarkers in melanoma, including BRAF, MMP2, p27, Dicer, Fbw7 and Tip60, our group has gone on to investigate if these markers are useful in risk stratification of melanoma patients in individual AJCC stages. First, we performed Kaplan-Meier survival and Cox proportional multivariate analyses comparing prognostication power of these markers in 254 melanoma patients for whom the expression levels were known, identifying the best performing markers as candidates for stage-specific melanoma markers. We then verified the results by incorporating an additional independent cohort (87 patients) and in a combined cohort (341 patients).Our data indicate that BRAF and MMP2 are optimal prognostic biomarkers for AJCC Stages I and II, respectively (P = 0.010, 0.000, Log-rank test); whereas p27 emerged as a good marker for AJCC Stages III/IV (0.018, 0.046, respectively, log-rank test). Thus, our study has identified stage-specific biomarkers in melanoma, a finding which may assist clinicians in designing improved personalized therapeutic modalities.