Torsten E. Reichert

Overexpression of Glut-1 and increased glucose metabolism in tumors are associated with a poor prognosis in patients with oral squamous cell carcinoma.

The overexpression of glucose transporters, especially of Glut‐1, is a common characteristic of human malignancies, including head and neck carcinoma. Recently, the assessment of glucose metabolism in the tumor with [18F]‐2‐fluoro‐2 deoxy‐D‐glucose (FDG) and positron emission tomography (FDG‐PET) has been used to identify particularly aggressive tumors. The authors tested the hypothesis that both glucose transport and its metabolism play a key role in the progression of oral squamous cell carcinoma (OSCC).

Defects in the Human Leukocyte Antigen Class I Antigen Processing Machinery in Head and Neck Squamous Cell Carcinoma: Association with Clinical Outcome

Purpose: Human leukocyte antigen (HLA) class I antigen defects, which are frequently present in head and neck squamous cell carcinoma (HNSCC) cells may provide the tumor with an escape mechanism from immune surveillance. Scanty information is available about mechanisms underlying HLA class I antigen defects in both lesions and cell lines from HNSCC. In this study, we investigate the role of antigen processing machinery (APM) component abnormalities in the generation of deficient HLA class I surface expression of HNSCC cells. Experimental Design: Using immunohistochemistry, Western blot, and RT-PCR analyses we correlated the expression of the IFN-γ inducible proteasome subunits and of the peptide transporter TAP with that of HLA class I antigens in biopsies and cell lines from primary, recurrent, and metastatic HNSCC. Furthermore, APM component and HLA class I antigen expression in surgically removed lesions were correlated with the course of the disease in order to assess the clinical significance of deficient expression of these molecules. Results: A high frequency of LMP2, LMP7, and TAP1 down-regulation or loss was found in tumor lesions and cell lines obtained from HNSCC cancer patients. These defects could be corrected by incubating cells with IFN-γ. Furthermore, LMP2, LMP7, TAP1, TAP2, and HLA class I antigen expression rates in primary HNSCC lesions were found to predict overall survival. Lastly, the level of LMP7 expression was significantly associated with disease recurrence at 2 years. Conclusions: Our results suggest that the analysis of APM component expression in HNSCC lesions can provide useful prognostic information in patients with HNSCC.

Somatic stem cells for regenerative dentistry

Complex human tissues harbour stem cells and/or precursor cells, which are responsible for tissue development or repair. Recently, dental tissues such as periodontal ligament (PDL), dental papilla or dental follicle have been identified as easily accessible sources of undifferentiated cells. The dental stem cell biology might provide meaningful insights into the development of dental tissues and cellular differentiation processes. Dental stem cells could also be feasible tools for dental tissue engineering. Constructing complex structures like a periodontium, which provides the functional connection between a tooth or an implant and the surrounding jaw, could effectively improve modern dentistry. Dental precursor cells are attractive for novel approaches to treat diseases like periodontitis, dental caries or to improve dental pulp healing and the regeneration of craniofacial bone and teeth. These cells are easily accessible and, in contrast to bone-marrow-derived mesenchymal stem cells, are more closely related to dental tissues. This review gives a short overview of stem cells of dental origin.

Clonal expansion of melan a-specific cytotoxic T lymphocytes in a melanoma patient responding to continued immunization with melanoma-associated peptides

Peptides derived from human tumor antigens have been used in a number of clinical trials to induce specific immune responses against autologous tumors in cancer patients. Although favorable clinical results were observed in single patients, immune responses correlating with tumor regression were either not detected or in case of responses, the T‐cell specificity was difficult to demonstrate. In this study, we analyzed antigen‐specific T‐cell responses induced in the skin and in peripheral blood lymphocytes (PBL) in an HLA‐A2‐positive melanoma patient. The patient showed major regression of metastatic melanoma under continued immunization with peptides derived from the melanocyte differentiation antigens Melan A/MART‐1, tyrosinase and gp100/Pmel17. Based on the identification of different T‐cell receptor (TCR) families reactive with Melan A/MART‐1, we have demonstrated that i.d. immunization with peptides alone leads to oligoclonal expansion of Melan A/MART‐1‐specific cytotoxic T lymphocytes (CTL), detectable in local delayed‐type hypersensitivity (DTH) reactions and PBL. A monoclonal expansion of a Melan A/MART‐1‐specific TCR VB 16 CTL was reproducibly observed after in vitro stimulation with Melan A/MART‐1 peptides. The same TCR VB 16 CTL clone was detected in skin biopsies taken from vitiligo areas. Our findings provide strong evidence for the effective induction of specific T‐cell responses to Melan A/MART‐1 by i.d. immunization with peptide alone, which accounts for dermal depigmentation, specific cytotoxicity against Melan A/MART‐1‐expressing melanoma cells and clinical tumor regression. Int. J. Cancer 86:538–547, 2000.

Effect of six different peri-implantitis disinfection methods on in vivo human oral biofilm

OBJECTIVE The aim of this human in vivo pilot study was to evaluate the efficacy of six antimicrobial agents on the surface decontamination of an oral biofilm attached to titanium implants. DESIGN For in vivo biofilm formation, we fixed titanium specimens to individual removable acrylic upper jaw splints (14 specimens in every splint), which were worn by four volunteers overnight for 12 h. The specimens were then treated with different antimicrobial agents for 1 min (Sodium hypochlorite, Hydrogen peroxide 3%, Chlorhexidingluconate 0.2%, Plax, Listerine, citric acid 40%). Afterwards, we quantified the total bacterial load and the viability of adhering bacteria by live or dead cell labelling in combination with fluorescence microscopy. RESULTS The total bacterial load on the titanium surfaces was significantly higher after incubation in the control solution phosphate-buffered saline (PBS) than after disinfection in sodium hypochlorite, hydrogen peroxide, chlorhexidine, Plax, Listerine, and citric acid. Furthermore, a significantly lower ratio between dead and total adhering bacteria (bactericidal effect) was found after incubation in control PBS, Plax mouth rinse, and citric acid than after incubation in sodium hypochlorite, hydrogen peroxide, chlorhexidine, and Listerine. CONCLUSIONS All tested antiseptics seem to be able to reduce the total amount of microorganisms accumulating on titanium surfaces. Furthermore, sodium hypochlorite, hydrogen peroxide, chlorhexidine, and Listerine showed a significant bactericidal effect against adhering bacteria.

Overexpression of EGFR and absence of C-KIT expression correlate with poor prognosis in salivary gland carcinomas

Aims:  To evaluate the prognostic impact of expression of receptor tyrosine kinases epidermal growth factor receptor (EGFR), HER2, and C‐KIT in relation to established clinicopathological parameters in salivary gland carcinomas.

Comparison of human dental follicle cells (DFCs) and stem cells from human exfoliated deciduous teeth (SHED) after neural differentiation in vitro

Dental stem cells from human exfoliated deciduous teeth (SHED) and dental follicle cells (DFCs) are neural crest-derived stem cells from human dental tissues. Interestingly, SHED and DFCs can successfully differentiate into neuron-like cells. We hypothesized that SHED and DFCs have the same neural cell differentiation potentials. To evaluate neural cell differentiation, we cultivated SHED and DFCs in four different serum-replacement media (SRMs) and analyzed cell morphology, cell proliferation, and gene expression patterns before and after differentiation. In a standard cell culture medium, SHED and DFCs have not only similar cell morphologies, but they also have similar gene expression patterns for known stem cell markers. However, only SHED expressed the neural stem cell marker Pax6. After cultivation in SRMs, cell proliferations of DFCs and SHED were reduced and the cell morphology was spindle-like with long processes. However, differentiated DFCs and SHED had different neural cell marker expression patterns. For example, gene expression of the late neural cell marker microtubule-associated protein 2 was upregulated in DFCs and downregulated in SHED in SRM with the B27 supplement. In contrast, SHED formed neurosphere-like cell clusters in SRM with the B27 supplement, epidermal growth factor, and fibroblast growth factor-2. Moreover, SHED differentially expressed the glial cell marker glial fibrillary acidic protein, which in contrast was weakly or not expressed in DFCs. In conclusion, SHED and DFCs have different neural differentiation potentials under the same cell culture conditions.

A Double‐Blind Randomized Controlled Trial (RCT) of Titanium‐13Zirconium versus Titanium Grade IV Small‐Diameter Bone Level Implants in Edentulous Mandibles – Results from a 1‐Year Observation Period

BACKGROUND The use of endosseous dental implants has become common practice for the rehabilitation of edentulous patients, and a two-implant overdenture has been recommended as the standard of care. The use of small-diameter implants may extend treatment options and reduce the necessity for bone augmentation. However, the mechanical strength of titanium is limited, so titanium alloys with greater tensile and fatigue strength may be preferable. PURPOSE This randomized, controlled, double-blind, multicenter study investigated in a split-mouth model whether small-diameter implants made from Titanium-13Zirconium alloy (TiZr, Roxolid™) perform at least as well as Titanium Grade IV implants. METHODS AND MATERIALS Patients with an edentulous mandible received one TiZr and one Ti Grade IV small-diameter bone level implant (3.3 mm, SLActive®) in the interforaminal region. The site distribution was randomized and double-blinded. Outcome measures included change in radiological peri-implant bone level from surgery to 12 months post-insertion (primary), implant survival, success, soft tissue conditions, and safety (secondary). RESULTS Of 91 treated patients, 87 were available for the 12-month follow-up. Peri-implant bone level change (-0.3 ± 0.5 mm vs -0.3 ± 0.6 mm), plaque, and sulcus bleeding indices were not significantly different between TiZr and Ti Grade IV implants. Implant survival rates were 98.9 percent and 97.8 percent, success rates were 96.6 percent and 94.4 percent, respectively. Nineteen minor and no serious adverse events were related to the study devices. CONCLUSION This study confirms that TiZr small-diameter bone level implants provide at least the same outcomes after 12 months as Ti Grade IV bone level implants. The improved mechanical properties of TiZr implants may extend implant therapy to more challenging clinical situations.

Bone formation and degradation of a highly porous biphasic calcium phosphate ceramic in presence of BMP-7, VEGF and mesenchymal stem cells in an ectopic mouse model

INTRODUCTION Angiogenesis and mesenchymal stem cells (MSCs) promote osteogenesis. The aim of the present study was to evaluate whether bone morphogenetic protein (BMP-7) promoted osteoinduction could be enhanced by combining it with vascular endothelial growth factor (VEGF) or MSCs in highly porous biphasic calcium phosphate (BCP) ceramics. MATERIALS AND METHODS BCP ceramic blocks were implanted in an ectopic site in 24 mice (BMP-7 vs. BMP-7/VEGF; BMP-7 vs. BMP-7/MSCs and BMP-7 vs. Control; each group n=8). Specimens were analysed 12 weeks after surgery by environmental scanning electron microscopy (ESEM) and Giemsa staining. RESULTS In all implanted scaffolds, newly formed bone was observed, even in the control site. No statistical differences in the amount of new bone were found in the presence of BMP-7 compared to BMP-7/VEGF (p=1.0) or BMP-7/MSCs (p=0.786). ESEM revealed a degradation of the scaffolds. A higher degradation was observed in areas where no bone-implant contact was present compared to areas where the ceramic was integrated in newly formed bone. CONCLUSIONS Neither VEGF nor MSCs enhanced BMP-7 induced bone formation under the selected conditions. The present ceramic seemed to be osteoinductive and degradable, making this material suitable for bone tissue engineering.

Detection of recurrent oral squamous cell carcinoma by [18F]-2-fluorodeoxyglucose-positron emission tomography: Implications for prognosis and patient management

Patients with recurrent oral squamous cell carcinoma (OSCC) have a dismal prognosis and represent a therapeutic challenge. A positron emission tomography (PET) scan with [18F]‐2‐fluorodeoxyglucose ([18F]FDG) can improve early cancer detection. The current study evaluates the prognostic value of [18F]FDG‐PET scan in patients with recurrent OSCC.