Medical-grade polycaprolactone scaffolds made by melt electrospinning writing for oral bone regeneration - a pilot study in vitro.

BACKGROUND: The spectrum of indications for the use of membranes and scaffolds in the field of oral and maxillofacial surgery includes, amongst others, guided bone regeneration (GBR). Currently available membrane systems face certain disadvantages such as difficult clinical handling, inconsistent degradation, undirected cell growth and a lack of stability that often complicate their application. Therefore, new membranes which can overcome these issues are of great interest in this field. METHODS: In this pilot study, we investigated polycaprolactone (PCL) scaffolds intended to enhance oral wound healing by means of melt electrospinning writing (MEW), which allowed for three-dimensional (3D) printing of micron scale fibers and very exact fiber placement. A singular set of box-shaped scaffolds of different sizes consisting of medical-grade PCL was examined and the scaffolds' morphology was evaluated via scanning electron microscopy (SEM). Each prototype sample with box sizes of 225 µm, 300 µm, 375 µm, 450 µm and 500 µm was assessed for cytotoxicity and cell growth by seeding each scaffold with human osteoblast-like cell line MG63. RESULTS: All scaffolds demonstrated good cytocompatibility according to cell viability, protein concentration, and cell number. SEM analysis revealed an exact fiber placement of the MEW scaffolds and the growth of viable MG63 cells on them. For the examined box-shaped scaffolds with pore sizes between 225 µm and 500 µm, a preferred box size for initial osteoblast attachment could not be found. CONCLUSIONS: These well-defined 3D scaffolds consisting of medical-grade materials optimized for cell attachment and cell growth hold the key to a promising new approach in GBR in oral and maxillofacial surgery.

Evaluation of miRNA-expression and clinical tumour parameters in oral squamous cell carcinoma (OSCC).

Squamous cell carcinoma of the head and neck (HNSCC) is the sixth most common malignancy worldwide. The past decades have not led to substantial improvement in diagnosis and therapy. Analysis of miRNA-expression may help to determine the progression profiles and outcomes of many different diseases, including HNSCC. Therefore, in this investigation, 43 formalin-fixed, paraffin-embedded (FFPE) samples of oral squamous cell carcinoma were micro-dissected, analysed for expression of 30 miRNAs and were compared with non-tumorous tissue. Furthermore, correlation analysis was performed, investigating possible correlations of miRNA-expression and patient or tumour-linked data, such as age, sex, tumour stage and size. miRNA extraction from FFPE samples functioned well for OSCC, and several miRNAs were differently expressed in tumours compared with non-tumorous tissue (i.e., miR-99*; miR-224; miR-205*), indicating their possible utility as biomarkers. Moreover, some miRNAs showed significant correlations with clinical and pathological data (e.g. tumour size: miR-3156, P = 0.033; T-stage: miR-212, P = 0.0009).

Stable fixation with absorbable sutures in craniofacial surgery.

The present study analyses the exclusive use of absorbable suture material (Vicryl(®), Ethicon, Germany) in the fixation of transposed bone segments in craniofacial surgery without modification of the osteotomy design. Among 129 children up to 24 months of age, osteosynthesis was conducted exclusively with Vicryl(®) sutures. The stability of postoperative results was evaluated and possible foreign body reactions were examined within the framework of clinical and radiological routine checks. All examined children exhibited stable postoperative conditions while the length of hospital stay was not affected. X-ray examinations of the skull in two planes demonstrated good bony union in all cases. Relevant foreign body reactions were not observed. The exclusive application of absorbable suture material enables stable and cost effective osteosynthesis. Significant foreign body reactions were not observed. The exclusive use of absorbable sutures did not alter the osteotomy design.

Expression of MAGE-A1-A12 subgroups in the invasive tumor front and tumor center in oral squamous cell carcinoma.

MAGE-A proteins are highly expressed in oral squamous cell carcinoma (OSCC) and are promising targets for cancer immunotherapy. This study examined the presence of MAGE-A expression within the tumor center (TC) and tumor invasive front (TIF) and evaluated its relationship to poor prognosis. The expression rate of each MAGE-A subtype, A1-A12, was examined in 68 OSCCs at the TIF and TC. Slides (1-µm) of tissue microarrays (diameter =0.6 mm) were immunohistochemically stained, and the findings were correlated to clinical data. Approximately 95% of the tumors had MAGE-A expression. Higher expression in the TC was shown significantly for MAGE-A1, -A5, -A6, -A9 and -A12 (P<0.05). MAGE-A2 and -A3 exhibited the opposite behavior (not significant, P>0.05). Age, tumor size, grade and survival time were not associated with the expression of certain MAGE-A subgroups. When expression in the whole tumor tissue was considered, only MAGE-A1 was expressed at a significantly higher rate in male patients (P=0.034). At the TIF, MAGE-A9 and the UICC disease stage were significantly correlated (P=0.0263), and MAGE-A6 and the UICC disease stage exhibited a strong trend (P=0.0596). The expression of MAGE-A3, -A4, -A5, -A9 and -A11 was significantly associated with lymph node metastasis, while MAGE-A4 was expressed in all regions of the tumors (TIF and TC). This study showed that higher expression of most MAGE-A antigens occurred at the TC rather than at the TIF. MAGE­A1, -A3, -A4, -A5, -A9 and -A11 were significantly associated with clinically advanced stages of disease and seem to be of particular interest.

Phosphorylated epidermal growth factor receptor expression and KRAS mutation status in salivary gland carcinomas.

OBJECTIVES: Salivary gland carcinomas (e.g., adenoidcystic carcinoma or mucoepidermoid carcinoma) are rare and often unresectable head and neck tumors. They are also weakly affected by most chemotherapeutic drugs, which emphasize the need for further studies on this topic. In clinical practice, various drugs target the well-characterized EGFR pathway in many epithelial tumors. There is limited reliable data on phophorylated EGFR expression, such as activated conformation, in salivary gland tumors. MATERIALS AND METHODS: This study investigates the pEGFR expression in salivary gland carcinomas (n = 43). Three different carcinoma varieties, that represent >50 % of all salivary gland tumors, were included: adenoidcystic carcinoma (n = 23), mucoepidermoid carcinoma (n = 17), and adenocarcinoma NOS (not otherwise specified) (n = 3). The specimens were investigated by immunohistochemistry. Additionally, mutations of KRAS oncogene were screened with gene sequencing. The findings were correlated with clinical data by using SPSS. RESULTS: In 34 out of 43 specimens (79 %), a positive staining for pEGFR was found. Sex, tumor entity, tumor site, and grading had no significant correlation with pEGFR expression. A weak correlation was found for tumor size and pEGFR expression. Significant correlations were found for pEGFR expression with patient's age and lymph node metastasis (pN). No specimen showed a KRAS mutation in codon 12 or 13. CONCLUSION: Salivary gland carcinomas show a high expression of pEGFR. This high expression correlates with lymph node metastasis, which supports the hypothesis that a high pEGFR expression facilitates lymphogenous metastasis. Due to this pEGFR expression, status may be a negative predictive factor in salivary gland carcinoma diagnostics. Patients with pN-positive salivary gland cancer may benefit from EGFR-inhibiting drugs. CLINICAL RELEVANCE: The EGFR pathway may be a potential target for chemotherapy of advanced unresectable salivary gland carcinomas.

Performance of cone beam computed tomography in comparison to conventional imaging techniques for the detection of bone invasion in oral cancer.

Detecting bone invasion in oral cancer is crucial for therapy planning and the prognosis. The present study evaluated cone beam computed tomography (CBCT) for detecting bone invasion in comparison to standard imaging techniques. A total of 197 patients with diagnoses of oral cancer underwent CBCT as part of preoperative staging between January 2007 and April 2013. The sensitivity, specificity, and accuracy of CBCT were compared with panoramic radiography (PR), multi-slice computed tomography (CT) or magnetic resonance imaging (MRI), and bone scintigraphy (BS) using McNemar's test. Histopathology and clinical follow-up served as references for the presence of bone invasion. CBCT and BS (84.8% and 89.3%, respectively), as well as CBCT and CT/MRI (83.2%), showed comparable accuracy (P = 0.188 and P = 0.771). CBCT was significantly superior to PR, which was reconstructed based on a CBCT dataset (74.1%, P = 0.002). In detecting bone invasion, CBCT was significantly more accurate than PR and was comparable to BS and CT/MRI. However, each method has certain advantages, and the best combination of imaging methods must be evaluated in prospective clinic trials.

Three-dimensional analysis of cranial growth from 6 to 12 months of age.

The aim of this study was to generate three-dimensional data of the physiological growth of the infant's cranium in the significant growth phase from 6 to 12 months of age. In a longitudinal observational study non-invasive 3D data using an optical surface scanner were generated of the entire head of 52 Caucasian infants (27 females and 25 males) between the ages of 6 (T1) and 12 (T2) months. The circumference of the head increased by 6.51 per cent (from 43.50 to 46.33cm). Analysis of width and length showed that the head grows 2.84 per cent more in length, resulting in a decrease in the cranial index of 2.52 per cent (from 83.87 to 81.76 per cent). The highest increment observed was in the total volume of the cranium, with an increase of 18.76 per cent (from 1229.01 to 1459.57cm(3)). Comparison of the left and right sides of the head by measuring the diagonal symmetry difference showed a difference of only 0.37cm. Overall, the symmetry-related parameters showed an almost symmetric development of the cranium in infants. The findings should provide valuable information on physiological growth and development of the infant's cranium. Therefore the high growth rate of the cranium in the first year of life suggests that this period is a critical period in which the disruption of developmental processes may have long-lasting effects on the morphology of the cranium with a prognostically unfavourable effect of the further growth of the viscerocranium.

Correlation of MAGE-A tumor antigens and the efficacy of various chemotherapeutic agents in head and neck carcinoma cells.

OBJECTIVES: The present study examined the relationship between MAGE-A tumor antigens and the efficacy of diamindichloridoplatin (DDP), 5-fluorouracil (5-FU), docetaxel, and paclitaxel for in vitro treatment of head and neck cancer. METHODS: In the present study, five cell lines of human squamous cell carcinomas were treated with DDP (25-400 µM), 5-FU (0.75-12 mM), docetaxel (1.56-25 nM), and paclitaxel (1.56-25 nM) for a period of 24 or 48 h. The efficacy of the agents was observed dynamically using real-time cell analysis. Subsequently, the expression levels of MAGE-A1, MAGE-A5, MAGE-A8, MAGE-A9, MAGE-A11, and MAGE-A12 were determined by quantitative real-time polymerase chain reaction. Chemosensitivity and MAGE-A-expression were correlated by linear regression. RESULTS: The tumor cell lines showed a highly differentiated response to the chemotherapeutic agents. Expression of MAGE-A11 was significantly associated with a poorer response to treatment with DDP, 5-FU, docetaxel, and paclitaxel. Two cell lines, one of which was MAGE-A11-positive, showed a significant and concentration-dependent cisplatin-induced growth spurt during the first 24 h after treatment. MAGE-A5 was connected to a positive effect on treatment with paclitaxel within the first 24 h after application. In association with docetaxel treatment, MAGE-A8 was connected to a poorer susceptibility. CONCLUSIONS: The results describe, for the first time, a correlation between these MAGE-A tumor antigens and the susceptibility of head and neck cancer cells to DDP, 5-FU, docetaxel, and paclitaxel. CLINICAL RELEVANCE: These findings could affect the antineoplastic treatment of patients with MAGE-A11-positive tumors.

Head orthesis therapy in infants with unilateral positional plagiocephaly: an interdisciplinary approach to broadening the range of orthodontic treatment.

OBJECTIVE: Unilateral positional plagiocephaly is the most common deformity of the head in infants. As part of a prospective controlled clinical study, the pathomorphology of the positional plagiocephaly in early infancy was examined. The goal was to use noninvasive three-dimensional (3D) imaging to generate, for the first time ever, a standard database of infants without head deformities, to quantify the asymmetry of the positional plagiocephaly, and to evaluate the effectiveness of functional growth control using head orthesis. PATIENTS AND METHODS: In the present study, 3D soft-tissue data of the entire head were collected from a total of 40 infants: 20 with positional plagiocephaly (6.0 ± 0.97 months) and 20 infants without a head deformity (6.4 ± 0.3 months). Functional growth was controlled using a custom-made head orthesis. To evaluate the therapy, pre- and posttherapeutic scans were evaluated in three dimensions. RESULTS: Compared with the control group, infants with positional plagiocephaly demonstrated a reduced maximum length of the head, an increased head height, a shift in the ear axis as well as asymmetric anterior and posterior volumes of the neurocranium in lateral comparisons. Therapy using head orthesis led to a significant improvement of the asymmetry, with a reduction of the diagonal difference and an adjustment of the posterior volumes. CONCLUSION: Conservative growth control of extrinsically deformed infant skulls represents an interdisciplinary medical expansion of the orthodontic therapeutic spectrum. To prevent potential effects of positional plagiocephaly on the viscerocranium, head orthesis therapy is advisable in infancy.

Identification of nonsteroidal antiinflammatory drug-induced gastroduodenal injury in children with juvenile rheumatoid arthritis.

In a cohort of children with juvenile rheumatoid arthritis treated with nonsteroidal antiinflammatory drugs and referred for gastrointestinal complaints, more than 75% had gastritis, antral erosions, or ulcers. Epigastric pain strongly correlated with documented gastroduodenal injury. Therapy with ranitidine or misoprostol led to clinical improvement. Nonsteroidal antiinflammatory drugs are associated with significant gastrointestinal abnormalities in children.

First pass effect of 1-naphthol in the gastric mucosa. Studies with isolated epithelium and cultured mucous cells of guinea pig.

Disposition of 1-[14C]naphthol was investigated in stripped gastric mucosal segments mounted in Ussing chambers. During 2-hr incubations, naphthol was glucuronidated (44-55% of added dose) and sulfated (7-15%). When naphthol was added to the luminal fluid at pH 7.0, conjugates were released with equal velocity to the luminal and to the vascular side, but with a luminal pH of 3, conjugates appeared predominantly on the vascular side. When naphthol was added to the vascular side (both sides pH 7), conjugates appeared predominantly on the vascular side. Cultured gastric mucous cells formed naphthol glucuronide and naphthol sulfate at a ratio of 9:1. These conjugates were transiently accumulated within cells up to 300-fold followed by slow release into the medium. In conclusion, the intact gastric mucosa is able to conjugate 1-naphthol at neutral and acidic luminal pH. The data suggest that ingested phenolic compounds might be modified by a gastric first pass effect.

Conjugation of 1-naphthol in the gastric mucosa of guinea pigs.

1-Naphthol was conjugated in tissue pieces of the gastric wall to naphthol glucuronide (85%) and naphthol sulfate (15%). There was no regioselectivity in different parts of the stomach. In separated gastric mucosal cell populations, the activities of both transferases were highest in the mucous cell fraction (apparent Vmax of glucuronidation: 0.83 nmol/mg protein/min; apparent Vmax of sulfation: 0.11) with only little, or no activity in chief cells and parietal cells. Immunohistochemically glucuronosyltransferase 1 was predominantly localized in surface mucous cells. In conclusion, the gastric mucosa is an important organ for phase II biotransformation.