Clinicopathologic and prognostic significance of SATB1 in cutaneous malignant melanoma

Background

Special AT-rich sequence-binding protein-1 (SATB1), a new type of gene regulator, has been reported to be expressed in several human cancers and may have malignant potential. However, no data on SATB1 expression and its relationship to tumor progression in cutaneous malignant melanoma (CMM) has yet been reported.

Objective

We examined the immunohistochemical expression of SATB1 in CMM to determine whether it could serve as a prognostic marker.

Methods

A total of 97 samples of primary CMM and controls were immunostained for SATB1. The following clinicopathologic variables were evaluated: age, gender, subtype, SATB1 expression, Breslow thickness, Clark level, presence of ulceration, lymph node metastasis, distant metastasis, and survival. Statistical analyses were performed to assess for associations. Several parameters were analyzed for survival using the Kaplan-Meier method and Cox proportional-hazards model.

Results

Forty cases (85.1%) of CMM showed positive staining for SATB1 by immunohistochemistry. The intensity of SATB1 staining was significantly higher in CMM than in nevus NV and normal skin (NS) (P < 0.01). High SATB1 expression was significantly correlated with Breslow thickness, Clark level, mortality, presence of ulceration, and lymph node metastasis (P < 0.01). Moreover, Kaplan-Meier analysis revealed that SATB1 overexpression was significantly associated with worse survival (P < 0.01). Further univariate analysis and multivariate regression analysis indicated that SATB1 expression was an independent prognostic marker for CMM (P = 0.03).

Conclusions

The overexpression of SATB1 correlated with metastatic potential of CMM and is a novel independent prognostic marker for predicting outcome.     

Strategic design to create HER2-targeting proteins with target-binding peptides immobilized on a fibronectin type III domain scaffold

Tumor-binding peptides such as human epidermal growth factor receptor 2 (HER2)-binding peptides are attractive therapeutic and diagnostic options for cancer. However, the HER2-binding peptides (HBPs) developed thus far are susceptible to proteolysis and lose their affinity to HER2 in vivo. In this report, a method to create a HER2-binding fluctuation-regulated affinity protein (HBP-FLAP) consisting of a fibronectin type III domain (FN3) scaffold with a structurally immobilized HBP is presented. HBPs were selected by phage-library screening and grafted onto FN3 to create FN3-HBPs, and the HBP-FLAP with the highest affinity (HBP sequence: YCAHNM) was identified after affinity maturation of the grafted HBP. HBP-FLAP containing the YCAHNM peptide showed increased proteolysis-resistance, binding to HER2 with a dissociation constant (K_D) of 58 nM in ELISA and 287 nM in biolayer interferometry and specifically detects HER2-expressing cancer cells. In addition, HBP-FLAP clearly delineated HER2-expressing tumors with a half-life of 6 h after intravenous injection into tumor-bearing mice. FN3-based FLAP is an excellent platform for developing target-binding small proteins for clinical applications.

A HER2-binding protein, HBP-FLAP, developed by peptide immobilization specifically binds to HER2 and has improved resistance to proteases.     

Fork injuries with the tines inserted bilaterally between the mandibular interdental spaces

In this paper, we report two rare cases of foreign body oral injuries caused by forks inserted tightly into both sides of the lingual interdental spaces between the mandibular deciduous canines and first deciduous molars (FDMs). These pediatric cases of foreign body insertion caused not only soft tissue injuries but also the potential luxation of affected deciduous teeth, i.e., the FDMs in the present cases, during the removal of the object by force.     

Fatigue resistance of yttria‐stabilized tetragonal zirconia polycrystal clasps for removable partial dentures

With the rapid development of computer‐aided design/computer‐aided manufacturing (CAD /CAM ) systems, the application of zirconia in removable partial dentures is expected to expand. Clasps composed of zirconia should improve esthetics without inducing the risk of metal allergy. The aim of this study was to examine the fatigue resistance of yttria‐stabilized tetragonal zirconia polycrystal (Y‐TZP) clasps for removable partial dentures. Yttria‐stabilized tetragonal zirconia polycrystal and cobalt‐chromium (Co‐Cr) alloy were prepared using CAD /CAM systems. Specimens were either of the semicircular type or of the flat type, with cross‐sectional areas of taper ratios of 0.50, 0.75, and 1.00. All specimens were tested using the cantilever test and the constant displacement fatigue test, and data were analyzed using ANOVA . During the cantilever test, the maximum displacement prior to fracture was greater than the required undercut, and the semicircular‐type specimen exhibited a higher fracture load than the flat type. None of the specimens displayed permanent deformation and showed almost the same degree of deformation after fatigue testing. A lower taper ratio was associated with lower average load values and greater displacement. Within the limitations of this study, it was possible to conclude that Y‐TZP provides the required undercut and adequate retentive force for removable partial denture clasps. Additionally, Y‐TZP and Co‐Cr alloy had almost the same degree of deformation even after the simulated lifespan of removable partial dentures.     

Prevalence and characteristics of chronic musculoskeletal pain in Japan: A second survey of people with or without chronic pain

Background

An epidemiological survey conducted in Japan in fiscal year 2010 revealed a high prevalence of chronic musculoskeletal pain, low patient satisfaction with treatment, a high incidence of protracted treatment lasting a year or more, and reduced quality of life. To improve the current system for treating chronic musculoskeletal pain, it is important to identify risk factors, including patient characteristics, for developing chronic pain. Thus, we sought to determine the incidence of new chronic pain in the Japanese population, as well as the persistence rate, associated factors, and current state of treatment of chronic pain, by repeating a postal survey in a nationwide representative sample group first surveyed in 2010.

Methods

Among 11,507 participants in the 2010 epidemiological survey, 1,717 reported chronic pain and 6,283 reported no chronic pain. A repeat questionnaire, mailed to subjects in these 2 groups in fiscal year 2011, received replies from 85 % of those who reported pain and 76 % of those without pain in 2010.

Results

The incidence of new chronic pain was 11.1 %. Risk factors for developing chronic pain included working in a professional, managerial, or clerical/specialist occupation, being female, having a BMI ≥25; currently using alcohol or cigarettes; and having completed an education level of vocational school or higher. Persistent chronic pain was reported by 45.2 % of respondents. Those with severe (VAS score ≥7) and constant lower-back pain lasting more than 5 years had the highest risk of the pain persisting. More than 80 % respondents with persistent chronic pain had a history of treatment, and while about 30 % were still receiving treatment at the time of the survey, the other 50 % had discontinued treatment despite the persistence of pain because of a low degree of satisfaction with treatment.

Discussion

We identified risk factors related to the development of new chronic pain and the persistence of chronic pain. Countermeasures to prevent chronic pain could be especially important for the high-risk populations for understanding the pathology of chronic pain.     

Use of inhaled fluticasone propionate to control respiratory manifestations of relapsing polychondritis

Effective management of respiratory tract involvement is very important in improving the prognosis of relapsing polychondritis (RPC). This case report describes a 19-year-old patient with RPC, who required frequent hospitalization due to recurrent exacerbations of airway obstruction. Use of high-dose fluticasone propionate effectively reduced the amount of oral corticosteroid necessary to control inflammation of the airway mucosa and dramatically decreased the patient's obstructive airway impairment. This report is the first illustrating the effectiveness and safety of inhaled corticosteroids in the control of the respiratory manifestations of RPC.     

Characterization of LLC-PK1 Kidney Epithelial Cells as an in Vitro Model for Studying Renal Tubular Reabsorption of Protein Drugs

Purpose. The purpose of this study was to assess whether LLC-PK₁ renal epithelial cells could serve as an in vitro model for studying the renal tubular reabsorption of protein drugs. Methods. The association of ¹¹¹In-labeled model protein drugs, bovine serum albumin (BSA), superoxide dismutase (SOD), soybean trypsin inhibitor (STI), and [Asu^1,7]-eel calcitonin (Asu-ECT), with the monolayers of LLC-PK₁ renal epithelial cells was characterized under various conditions. Results. The cellular association of these proteins was temperature-dependent and varied according to the protein. Saturation kinetics were observed for STI association, with the apparent Km and Vmax values determined to be 66.3 µg/ml and 250 ng/mg protein/min, respectively. The association of STI decreased with increases in medium pH from 5.4 to 8.4 and was inhibited significantly by 2,4-dinitrophenol, sodium azide, cytochalasin B, and colchicine, suggesting that the cellular association involved endocytosis. Mutual inhibition was observed in competitive binding experiments with the four protein drugs, suggesting that they shared a common binding site on the luminal membrane of LLC-PK₁ cells. Taken together, these findings show that a variety of protein drugs bind to LLC-PK₁ cells in a non-specific manner and possibly undergo endocytosis, a phenomenon that is similar to in vivo proximal tubular reabsorption. Conclusions. LLC-PK₁ renal epithelial cells would be a suitable model system for the study of the renal proximal tubular reabsorption of protein drugs.     

Long-term monitoring of IOX4 in horse hair and its longitudinal distribution with segmental analysis using liquid chromatography/electrospray ionization Q Exactive high-resolution mass spectrometry for the purpose of doping control

IOX4, a hypoxia-inducible factor stabilizer, is classified as a banned substance for horses in both horse racing and equestrian sports. We recently reported the pharmacokinetic profiles of IOX4 in horse plasma and urine and also identified potential monitoring targets for the doping control purpose. In this study, a long-term longitudinal analysis of IOX4 in horse hair after a nasoesophageal administration of IOX4 (500 mg/day for 3 days) to three thoroughbred mares is presented for the first time for controlling the abuse/misuse of IOX4. Six bunches of mane hair were collected at 0 (pre), 1, 2, 3, and 6 month(s) postadministration. Our results showed that the presence of IOX4 was identified in all postadministration horse hair samples, but no metabolite could be detected. The detection window for IOX4 could achieve up to 6-month postadministration (last sampling point) by monitoring IOX4 in hair. In order to evaluate the longitudinal distribution of IOX4 over 6 months, a validated quantification method of IOX4 in hair was developed for the analysis of the postadministration samples. Segmental analysis of 2-cm cut hair across the entire length of postadministration hair showed that IOX4 could be quantified up to the level of 1.84 pg/mg. In addition, it was found that the movement of the incorporated IOX4 band in the hair shaft over 6 months varied among the three horses due to individual variation and a significant diffusion of IOX4 band up to 10 cm width was also observed in the 6-month postadministration hair samples.