Preliminary data on Pemphigus vulgaris treatment by a proteomics-defined peptide: a case report

Background

A functional blood supply is essential for tumor growth and proliferation. However, the mechanism of blood vessel recruitment to the tumor is still poorly understood. Ideally, a thorough molecular assessment of blood vessel cells would be critical in our comprehension of this process. Yet, to date, there is little known about the molecular makeup of the endothelial cells of tumor-associated blood vessels, due in part to the difficulty of isolating a pure population of endothelial cells from the heterogeneous tissue environment.

Methods

Here we describe the use of a recently developed technique, Expression Microdissection, to isolate endothelial cells from the tumor microenvironment. The methylation status of the dissected samples was evaluated for GSTP1 and RARβ2 promoters via the QMS-PCR method.

Results

Comparing GSTP1 and RARβ2 promoter methylation data, we show that 100% and 88% methylation is detected, respectively, in the tumor areas, both in epithelium and endothelium. Little to no methylation is observed in non-tumor tissue areas.

Conclusion

We applied an accurate microdissection technique to isolate endothelial cells from tissues, enabling DNA analysis such as promoter methylation status. The observations suggest that epigenetic alterations may play a role in determining the phenotype of tumor-associated vasculature.     

Pediatric reference values for urine particle quantification by using automated flow cytometer: Results of a multicenter study of Italian urinalysis group

Objectives

The purpose of this Italian multicenter study was to define pediatric upper reference values for urine particle quantification by using automated flow cytometry.

Design and methods

Four hospital-based clinical laboratories participated in this multicenter investigation, which included a total study population of 161 Italian children aged from 1 to 12 years. Two laboratories used Sysmex UF-100 and analyzed 86 children, whereas the other two used Sysmex UF-1000i and analyzed 75 subjects. Particle quantification included the analysis of white blood cells (WBC), red blood cells (RBC), squamous epithelial cells (EC), transitional epithelial cells (TC), casts (CAST) and bacteria (BACT).

Results

The upper reference values in subjects tested with the Sysmex UF-100 were 9.7 WBC/μL, 10.1 RBC/μL, 7.5 EC/μL, 2.5 TC/μL, 0.7 CAST/μL and 3090 BACT/μL, whereas the upper reference values in subjects tested with the Sysmex UF-1000i were 10.5 WBC/μL, 8.3 RBC/μL, 7.2 EC/μL, 2.9 TC/μL, 0.7 CAST/μL and 48 BACT/μL. No statistically significant differences between genders were found in the value distribution of any of the parameters tested. Similarly, no statistically significant differences were observed between the two urine analyzers, except for BACT.

Conclusions

Automated analysis of urine particles appears a suitable means to optimize the workflow of routine urinalysis of children specimens. The upper reference limits for pediatric subjects obtained in this study were comparable to those previously reported in the literature, with no significant differences between genders and analyzers.     

Praxic and executive components in tool use learning: the role of imitation

Recent research in comparative psychology suggests that similarities between the behaviour of two individuals may not be the consequence of imitation only, but also of nonimitative social-learning processes. In the present study we aimed to investigate whether these alternative learning processes can take place in human adults, specifically in patients whose ability to imitate has been reduced by brain damage. Left (LBD) and right (RBD) brain-damaged patients were asked to perform four tool use tasks in three experimental conditions: exposure to the apparatus (N); demonstration of the correct solution (C); and demonstration of a failed attempt followed by the correct solution to the problem (I + C). Results suggest that the left hemisphere is indeed critical for action and that selective neuropsychological deficits can affect action imitation and selection of goal-directed movements, independently from each other. Findings also indicate that when the ability to imitate actions is lowered emulation may become available.     

Radioembolisation in patients with hepatocellular carcinoma that have previously received liver-directed therapies

Purpose

Radioembolisation is part of the multimodal treatment of hepatocellular carcinoma (HCC) at specialist liver centres. This study analysed the impact of prior treatment on tolerability and survival following radioembolisation.

Methods

This was a retrospective analysis of 325 consecutive patients with a confirmed diagnosis of HCC, who received radioembolisation with yttrium-90 resin microspheres at eight European centres between September 2003 and December 2009. The decision to treat was based on the clinical judgement of multidisciplinary teams. Patients were followed from the date of radioembolisation to last contact or death and the nature and severity of all adverse events (AEs) recorded from medical records.

Results

Most radioembolisation candidates were Child-Pugh class A (82.5%) with multinodular HCC (75.9%) invading both lobes (53.1%); 56.3% were advanced stage. Radioembolisation was used first-line in 57.5% of patients and second-line in 34.2%. Common prior procedures were transarterial (chemo)embolisation therapies (27.1%), surgical resection/transplantation (17.2%) and ablation (8.6%). There was no difference in AE incidence and severity between prior treatment subgroups. Median (95% confidence interval [CI]) survival following radioembolisation was similar between procedure-naive and prior treatment groups for Barcelona Clinic Liver Cancer (BCLC) stage A: 22.1 months (15.1–45.9) versus 30.9 months (19.6–46.8); p?= 0.243); stage B: 18.4 months (11.2–19.4) versus 22.8 months (10.9–34.2); p?= 0.815; and stage C: 8.8 months (7.1–10.8) versus 10.8 months (7.7–12.6); p?= 0.976.

Conclusions

Radioembolisation is a valuable treatment option for patients who relapse following surgical, ablative or vascular procedures and remain suitable candidates for this treatment.

     

Amino acid metabolism as drug target in autoimmune diseases

In mammals, amino acid metabolism has evolved to control immune responses. Autoimmune diseases are heterogeneous conditions that involve the breakdown of tolerogenic circuitries and consequent activation of autoreactive immune cells. Therefore, critical enzymes along amino acid degradative pathways may be hijacked to keep in check autoimmunity. We examined here current knowledge of indoleamine 2,3-dioxygenase 1 (IDO1) and arginase 1 (ARG1), the main enzymes catabolizing tryptophan and arginine, respectively, in organ-specific and systemic autoimmune diseases as well as in the development of autoantibodies to therapeutic proteins. At variance with neoplastic contexts, in which it is known to act as a pure immunosuppressive molecule, ARG1 exhibited a protective or pathogenetic profile, depending on the disease. In contrast, in several autoimmune conditions, the bulk of data indicated that drugs capable of potentiating IDO1 expression and activity may represent valuable therapeutic tools and that IDO1-based immunotherapeutic protocols could be more effective if tailored to the genetic profile of individual patients.