A. Rittig

Expression Profile of Human Beta-Defensin 3 in Oral Squamous Cell Carcinoma

Although it is known that innate immunity is important for protecting the body against foreign agents such as bacteria, little is known about elements of the innate immune system that have antitumor activity. This prospective study was designed to investigate the function of human beta-defensin 3 (hBD-3), an important component of the innate immune response, in oral squamous cell carcinoma (OSCC). Paired cancerous and noncancerous specimens of 45 patients who underwent surgical treatment for OSCC were examined for hBD-3 expression on protein and mRNA. Clinical and pathological features such as age, gender, tumor and lymph node status, UICC stage, and histological grading were correlated. hBD-3 was significantly overexpressed in tumors in comparison to healthy tissue examined with real-time quantitative reverse transcriptase–polymerase chain reaction (qRT-PCR) analysis (p = .004). Immunohistochemical stain for hBD-3 was much more pronounced in tumors than in corresponding healthy mucosa. The results illustrate that hBD-3 is frequently overexpressed in oral squamous cell carcinomas and seems to be related to oncogenesis. Increased expression of hBD-3 in oral squamous cell carcinomas suggests its potential role in the pathogenesis of oral cancer. This might be a starting point for novel pharmacological/molecular treatment modalities.

Vergleichende In-vitro-Studie zur Zytotoxizität klinisch eingesetzter Antiseptika

ZusammenfassungHintergrundAntiseptika zur Behandlung chronischer und infizierter Wunden gehören zur Standardtherapie. Erkenntnisse über toxische Eigenschaften gegenüber dem Wund- und Hautgewebe sind jedoch kaum vorhanden. Diese Studie untersucht den Einfluss von Wundantiseptika auf die Vitalität und Proliferation humaner kutaner Zellen.Material und MethodenDie Antiseptika Lavasept (PHMB), Octenisept (Octenidin) und Betaisodona (PVP-Jod) wurden mittels MTT-Assay und BrDU-ELISA auf zytotoxische Effekte gegenüber der HaCaT-Zelllinie, primären humanen Keratinozyten und Fibroblasten untersucht.ErgebnisseLavasept besaß nur geringen Einfluss auf Vitalität und Zellproliferation. Betaisodona und Octenisept induzierten eine signifikante Reduktion der Zellvitalität (p<0,05) bis zu 0% überlebender Fibroblasten bei 7,5% (Betaisodona) bzw. 10% (Octenisept) sowie der Zellproliferation auf 0% bei Keratinozyten durch Konzentrationen von 7,5% (Betaisodona und Octenisept).SchlussfolgerungDie Studie zeigt, dass herkömmlich verwendete Wundantiseptika deutlich toxische Effekte besitzen. Sowohl antimikrobielle Potenz als auch toxische Eigenschaften der einzelnen Antiseptika müssen bei der Wundbehandlung berücksichtigt werden. Insgesamt zeigte die PHMB-Lösung (Lavasept) die geringste toxische Wirkung.AbstractPurposeLocal skin antiseptics are the standard of care for chronic and non-healing wounds. However, little is known about their potential toxic properties. This study investigates the impact of three commercially available and widely used antiseptics on vitality and proliferation of human cutaneous cells.Material and MethodsThree antiseptics, Lavasept (PHMB), Octenisept (octenidine) and Betaisodona (PVP-iodine) were tested for their cytotoxic effects towards HaCaT cells, primary human keratinocytes and fibroblasts using MTT assay and BrDU ELISA.ResultsLavasept showed only slight to moderate toxic effects on cellular vitality and proliferation. Ocentisept and Betaisodona induced severe reduction of cell vitality (p<0.05) to 0% surviving fibroblasts at 7.5% (Betaisodona) and 12.5% Octenisept, respectively. Furthermore, poliferative activity was reduced to 0% in keratinocytes at 7.5% concentration of Betaisodona and Ocentisept.ConclusionThis study shows that frequently used wound- and skin antiseptics show severe cytotoxic effects towards cutaneous cells. Furthermore, antimicrobial efficacy and toxic properties must be included in the clinical decision process for optimal therapy of chronic wounds. The PHMB solution Lavasept showed best results regarding toxicity in this study.PURPOSE Local skin antiseptics are the standard of care for chronic and non-healing wounds. However, little is known about their potential toxic properties. This study investigates the impact of three commercially available and widely used antiseptics on vitality and proliferation of human cutaneous cells. MATERIAL AND METHODS Three antiseptics, Lavasept (PHMB), Octenisept (octenidine) and Betaisodona (PVP-iodine) were tested for their cytotoxic effects towards HaCaT cells, primary human keratinocytes and fibroblasts using MTT assay and BrDU ELISA. RESULTS Lavasept showed only slight to moderate toxic effects on cellular vitality and proliferation. Ocentisept and Betaisodona induced severe reduction of cell vitality (p<0.05) to 0% surviving fibroblasts at 7.5% (Betaisodona) and 12.5% Octenisept, respectively. Furthermore, poliferative activity was reduced to 0% in keratinocytes at 7.5% concentration of Betaisodona and Ocentisept. CONCLUSION This study shows that frequently used wound- and skin antiseptics show severe cytotoxic effects towards cutaneous cells. Furthermore, antimicrobial efficacy and toxic properties must be included in the clinical decision process for optimal therapy of chronic wounds. The PHMB solution Lavasept showed best results regarding toxicity in this study.

A comparative in vitro study of cell toxicity of clinically used antiseptics

ZusammenfassungHintergrundAntiseptika zur Behandlung chronischer und infizierter Wunden gehören zur Standardtherapie. Erkenntnisse über toxische Eigenschaften gegenüber dem Wund- und Hautgewebe sind jedoch kaum vorhanden. Diese Studie untersucht den Einfluss von Wundantiseptika auf die Vitalität und Proliferation humaner kutaner Zellen.Material und MethodenDie Antiseptika Lavasept (PHMB), Octenisept (Octenidin) und Betaisodona (PVP-Jod) wurden mittels MTT-Assay und BrDU-ELISA auf zytotoxische Effekte gegenüber der HaCaT-Zelllinie, primären humanen Keratinozyten und Fibroblasten untersucht.ErgebnisseLavasept besaß nur geringen Einfluss auf Vitalität und Zellproliferation. Betaisodona und Octenisept induzierten eine signifikante Reduktion der Zellvitalität (p<0,05) bis zu 0% überlebender Fibroblasten bei 7,5% (Betaisodona) bzw. 10% (Octenisept) sowie der Zellproliferation auf 0% bei Keratinozyten durch Konzentrationen von 7,5% (Betaisodona und Octenisept).SchlussfolgerungDie Studie zeigt, dass herkömmlich verwendete Wundantiseptika deutlich toxische Effekte besitzen. Sowohl antimikrobielle Potenz als auch toxische Eigenschaften der einzelnen Antiseptika müssen bei der Wundbehandlung berücksichtigt werden. Insgesamt zeigte die PHMB-Lösung (Lavasept) die geringste toxische Wirkung.AbstractPurposeLocal skin antiseptics are the standard of care for chronic and non-healing wounds. However, little is known about their potential toxic properties. This study investigates the impact of three commercially available and widely used antiseptics on vitality and proliferation of human cutaneous cells.Material and MethodsThree antiseptics, Lavasept (PHMB), Octenisept (octenidine) and Betaisodona (PVP-iodine) were tested for their cytotoxic effects towards HaCaT cells, primary human keratinocytes and fibroblasts using MTT assay and BrDU ELISA.ResultsLavasept showed only slight to moderate toxic effects on cellular vitality and proliferation. Ocentisept and Betaisodona induced severe reduction of cell vitality (p<0.05) to 0% surviving fibroblasts at 7.5% (Betaisodona) and 12.5% Octenisept, respectively. Furthermore, poliferative activity was reduced to 0% in keratinocytes at 7.5% concentration of Betaisodona and Ocentisept.ConclusionThis study shows that frequently used wound- and skin antiseptics show severe cytotoxic effects towards cutaneous cells. Furthermore, antimicrobial efficacy and toxic properties must be included in the clinical decision process for optimal therapy of chronic wounds. The PHMB solution Lavasept showed best results regarding toxicity in this study.PURPOSE Local skin antiseptics are the standard of care for chronic and non-healing wounds. However, little is known about their potential toxic properties. This study investigates the impact of three commercially available and widely used antiseptics on vitality and proliferation of human cutaneous cells. MATERIAL AND METHODS Three antiseptics, Lavasept (PHMB), Octenisept (octenidine) and Betaisodona (PVP-iodine) were tested for their cytotoxic effects towards HaCaT cells, primary human keratinocytes and fibroblasts using MTT assay and BrDU ELISA. RESULTS Lavasept showed only slight to moderate toxic effects on cellular vitality and proliferation. Ocentisept and Betaisodona induced severe reduction of cell vitality (p<0.05) to 0% surviving fibroblasts at 7.5% (Betaisodona) and 12.5% Octenisept, respectively. Furthermore, poliferative activity was reduced to 0% in keratinocytes at 7.5% concentration of Betaisodona and Ocentisept. CONCLUSION This study shows that frequently used wound- and skin antiseptics show severe cytotoxic effects towards cutaneous cells. Furthermore, antimicrobial efficacy and toxic properties must be included in the clinical decision process for optimal therapy of chronic wounds. The PHMB solution Lavasept showed best results regarding toxicity in this study.

Human β-defensin-3 correlates with muscle fibre degeneration in idiopathic inflammatory myopathies

Sporadic inclusion body myositis (sIBM) and polymyositis (PM) are characterized by muscle inflammation, with sIBM showing additional degenerative alterations. In this study we investigated human beta defensins and associated TLRs to elucidate the role of the innate immune system in idiopathic inflammatory myopathies (IIM), and its association with inflammatory and degenerative alterations. Expression levels of human beta-defensin (HBD)-1, HBD-2, HBD-3 and TLR2, 3, 4, 7 and 9 were analysed by quantitative real-time PCR in skeletal muscle tissue. Localization of HBD-3, collagen 6, dystrophin, CD8-positive T-cells, CD-68-positive macrophages, β-amyloid, the autophagy marker LC3, and TLR3 were detected by immunofluorescence and co-localization was quantified. HBD-3 and all TLRs except for TLR9 were overexpressed in both IIM with significant overexpression of TLR3 in sIBM. HBD-3 showed characteristic intracellular accumulations near deposits of β-amyloid, LC3 and TLR3 in sIBM, and was detected in inflammatory infiltrations and macrophages invading necrotic muscle fibres in both IIM. The characteristic intracellular localization of HBD-3 near markers of degeneration and autophagy, and overexpression of endosomal TLR3 in sIBM hint at different pathogenetic mechanisms in sIBM compared with PM. This descriptive study serves as a first approach to the role of the innate immune system in sIBM and PM.

EPHB4 tyrosine-kinase receptor expression and biological significance in soft tissue sarcoma

Soft tissue sarcomas (STS) are heterogeneous malignant tumors of mesenchymal origin. Due to low incidence and high number of different histological subtypes, their pathogenesis and thus potential targets for their therapy remain barely investigated. Several studies revealed significant higher EPHB4 expression in malignancies such as prostate and colorectal cancer showing survival advantages for these tumor cells. Therefore we studied the expression of EPHB4 in a total of 46 clinical human specimens of different STS and human fibroblasts. EPHB4 mRNA and protein expression were significantly increased in synovial sarcoma. After targeting EPHB4 in fibrosarcoma, synovial sarcoma, liposarcoma and MFH sarcoma cell lines by siRNA or by inhibition of autophosphorylation using the specific EPHB4 kinase inhibitor NVP‐BHG712 a decreased proliferation rate/vitality of synovial‐ and fibrosarcoma cells was observed. Silencing of EPHB4 significantly reduced the transmigration of synovial sarcoma cells towards fibroblasts and endothelial cells. In addition, we assessed the anti‐metastatic effect of EPHB4 inhibition in vivo by intraperitoneal administration of the EPHB4 inhibitor in an appropriate sarcoma lung metastasis xenograft model. As result 43% of NVP‐BHG712 treated mice (n = 3/7) developed pulmonary metastases whereas all control mice (n = 5) revealed lung metastases. The residual 57% of mice (n = 4/7) showed only small local tumor cell spots. Size measurements of the Vimentin positive area explained significant decrease in lung metastasis formation (p < 0.05) after EPHB4 kinase inhibition. In summary, these data provide first evidence of the importance of EPHB4 in the tumorigenesis of synovial sarcoma and present EPHB4 as a potential target in the therapy of this malignancy.

Vergleichende In-vitro-Studie zur Zytotoxizität klinisch eingesetzter Antiseptika@@@A comparative in vitro study of cell toxicity of clinically used antiseptics

ZusammenfassungHintergrundAntiseptika zur Behandlung chronischer und infizierter Wunden gehören zur Standardtherapie. Erkenntnisse über toxische Eigenschaften gegenüber dem Wund- und Hautgewebe sind jedoch kaum vorhanden. Diese Studie untersucht den Einfluss von Wundantiseptika auf die Vitalität und Proliferation humaner kutaner Zellen.Material und MethodenDie Antiseptika Lavasept (PHMB), Octenisept (Octenidin) und Betaisodona (PVP-Jod) wurden mittels MTT-Assay und BrDU-ELISA auf zytotoxische Effekte gegenüber der HaCaT-Zelllinie, primären humanen Keratinozyten und Fibroblasten untersucht.ErgebnisseLavasept besaß nur geringen Einfluss auf Vitalität und Zellproliferation. Betaisodona und Octenisept induzierten eine signifikante Reduktion der Zellvitalität (p<0,05) bis zu 0% überlebender Fibroblasten bei 7,5% (Betaisodona) bzw. 10% (Octenisept) sowie der Zellproliferation auf 0% bei Keratinozyten durch Konzentrationen von 7,5% (Betaisodona und Octenisept).SchlussfolgerungDie Studie zeigt, dass herkömmlich verwendete Wundantiseptika deutlich toxische Effekte besitzen. Sowohl antimikrobielle Potenz als auch toxische Eigenschaften der einzelnen Antiseptika müssen bei der Wundbehandlung berücksichtigt werden. Insgesamt zeigte die PHMB-Lösung (Lavasept) die geringste toxische Wirkung.AbstractPurposeLocal skin antiseptics are the standard of care for chronic and non-healing wounds. However, little is known about their potential toxic properties. This study investigates the impact of three commercially available and widely used antiseptics on vitality and proliferation of human cutaneous cells.Material and MethodsThree antiseptics, Lavasept (PHMB), Octenisept (octenidine) and Betaisodona (PVP-iodine) were tested for their cytotoxic effects towards HaCaT cells, primary human keratinocytes and fibroblasts using MTT assay and BrDU ELISA.ResultsLavasept showed only slight to moderate toxic effects on cellular vitality and proliferation. Ocentisept and Betaisodona induced severe reduction of cell vitality (p<0.05) to 0% surviving fibroblasts at 7.5% (Betaisodona) and 12.5% Octenisept, respectively. Furthermore, poliferative activity was reduced to 0% in keratinocytes at 7.5% concentration of Betaisodona and Ocentisept.ConclusionThis study shows that frequently used wound- and skin antiseptics show severe cytotoxic effects towards cutaneous cells. Furthermore, antimicrobial efficacy and toxic properties must be included in the clinical decision process for optimal therapy of chronic wounds. The PHMB solution Lavasept showed best results regarding toxicity in this study.PURPOSE Local skin antiseptics are the standard of care for chronic and non-healing wounds. However, little is known about their potential toxic properties. This study investigates the impact of three commercially available and widely used antiseptics on vitality and proliferation of human cutaneous cells. MATERIAL AND METHODS Three antiseptics, Lavasept (PHMB), Octenisept (octenidine) and Betaisodona (PVP-iodine) were tested for their cytotoxic effects towards HaCaT cells, primary human keratinocytes and fibroblasts using MTT assay and BrDU ELISA. RESULTS Lavasept showed only slight to moderate toxic effects on cellular vitality and proliferation. Ocentisept and Betaisodona induced severe reduction of cell vitality (p<0.05) to 0% surviving fibroblasts at 7.5% (Betaisodona) and 12.5% Octenisept, respectively. Furthermore, poliferative activity was reduced to 0% in keratinocytes at 7.5% concentration of Betaisodona and Ocentisept. CONCLUSION This study shows that frequently used wound- and skin antiseptics show severe cytotoxic effects towards cutaneous cells. Furthermore, antimicrobial efficacy and toxic properties must be included in the clinical decision process for optimal therapy of chronic wounds. The PHMB solution Lavasept showed best results regarding toxicity in this study.