A Berndt

Publications (61)129.66 Total impact

• Article: Emergency and therapeutic vaccination--is stimulating innate immunity an option?

  N Foster, A Berndt, A-C Lalmanach, U Methner, P Pasquali, I Rychlik, P Velge, X Zhou, P Barrow
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  ABSTRACT: There is increasing evidence that activation of innate immunity, in animals and man, by live vaccines, sub-unit vaccines or synthetic or non-synthetic stimulants can induce a profound and rapidly induced resistance to pathogens, including infectious agents that are unrelated to the stimulating antigen or agent. We review the evidence for this phenomenon and present the proposition that this approach might be used to stimulate immunity during the life of the animal when susceptibility to infection is high and when normal vaccination procedures may be inappropriate.
  Research in Veterinary Science 10/2011; 93(1):7-12. · 1.65 Impact Factor
• Article: B domain containing Tenascin-C: a new urine marker for surveillance of patients with urothelial carcinoma of the urinary bladder?

  T Gecks, K Junker, M Franz, P Richter, M Walther, A Voigt, D Neri, H Kosmehl, H Wunderlich, M Kiehntopf, A Berndt
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  ABSTRACT: ECM remodelling during tumorigenesis entails the re-occurrence of different Tn-C(L) splicing variants. In patients with urothelial carcinoma of the urinary bladder (UBC), B and C domain containing Tenascin-C (B(+) and C(+) Tn-C) urine levels were shown to be increased in case of muscle invasiveness. Thus, the present study was aimed at examining the ability of B(+) and C(+) Tn-C as potential urinary surveillance markers of UBC patients. Urine levels of B(+) and C(+) Tn-C were determined by ELISA in 35 UBC patients during a 2 year follow-up period after therapy and related to clinical diagnosis and histological stage in 4 defined groups representing typical courses of disease. B(+) Tn-C levels showed significant differences between cases of tumour progression or regression. The urine levels of B(+) Tn-C could be used to discriminate between cases without tumour recurrence and such with tumour existence (cut-off value: 0.8 ng/ml) or between non-muscle invasive and muscle invasive tumour growth (cut-off value: 3.5 ng/ml). Progression of UBC with time is accompanied by significant changes in urinary levels of B(+) Tn-C. Urinary B(+) Tn-C can therefore be suggested as a valuable urine surveillance marker in UBC follow-up care.
  Clinica chimica acta; international journal of clinical chemistry 10/2011; 412(21-22):1931-6. · 2.54 Impact Factor
• Article: Exploitation of intestinal colonization-inhibition between salmonella organisms for live vaccines in poultry: potential and limitations.

  U Methner, A Haase, A Berndt, G Martin, B Nagy, P A Barrow
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  ABSTRACT: Immunization represents one of the most important methods to increase the resistance of chickens against Salmonella infection. In addition to the development of an adaptive immune response, oral administration of live Salmonella strains to day-old chicks provides protection against infection within hours by intestinal colonization-inhibition. For the exploitation of this phenomenon, practical information on colonization-inhibition between Salmonella organisms is needed. Colonization-inhibition capacity between Salmonella strains from serogroups B, C1, C2, D and G was assessed in chickens. The most profound level of intestinal colonization-inhibition occurred between isogenic strains. Inhibition between strains of the same serovar was greater than that between strains of different serovars. The degree of inhibition between different serovars was not sufficiently high to identify a single strain which might inhibit a wide range of other Salmonella organisms. However, as Salmonella Enteritidis is the dominant serovar in poultry in many countries and because of the profound colonization-inhibition within this serovar there is a considerable potential to exploit this phenomenon in the development of novel live S. Enteritidis vaccines. Treatment of young chicks with mixtures of different Salmonella serovars resulted not only in a very strong growth inhibition of the isogenic strains but also in a substantial inhibition of heterologous serovars. The potential of mixtures of heterologous Salmonella strains as a 'Salmonella Inhibition Culture' and as a 'live Salmonella vaccine' should be further explored.
  Zoonoses and Public Health 04/2011; 58(8):540-8. · 1.89 Impact Factor
• Article: Extra cellular matrix remodelling after heterotopic rat heart transplantation: gene expression profiling and involvement of ED-A+ fibronectin, alpha-smooth muscle actin and B+ tenascin-C in chronic cardiac allograft rejection.

  Marcus Franz, K Grün, P Richter, B R Brehm, M Fritzenwanger, K Hekmat, D Neri, J Gummert, H R Figulla, H Kosmehl, A Berndt, A Renner
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  ABSTRACT: Chronic cardiac rejection is represented by cardiac allograft vasculopathy (CAV) and cardiac interstitial fibrosis (CIF) known to cause severe complications. These processes are accompanied by remarkable changes in the cardiac extra cellular matrix (cECM). The aim of our study was to analyse the cECM remodelling in chronic rejection and to elucidate a potential role of ED-A domain containing fibronectin (ED-A(+) Fn), alpha smooth muscle actin (ASMA) and B domain containing tenascin-C (B(+) Tn-C). A model of chronic rejection after heterotopic rat heart transplantation was used. Allografts, recipient and control hearts were subjected to histological assessment of rejection grade, to real-time PCR based analysis of 84 genes of ECM and adhesion molecules and to immunofluorescence labelling procedures, including ED-A(+) Fn, ASMA and B(+) Tn-C antibodies. Histological analysis revealed different grades of chronic rejection. By gene expression analysis, a relevant up-regulation of the majority of ECM genes in association with chronic rejection could be shown. For 8 genes, there was a relevant up-regulation in allografts as well as in the corresponding recipient hearts. Association of ASMA positive cells with the grade of chronic rejection could be proven. In CAV and also in CIF there were extensive co-depositions of ED-A(+) Fn, ASMA and B(+) Tn-C. In conclusion, chronic cardiac allograft rejection is associated with a cECM remodelling. ASMA protein deposition in CAV, and CIF is a valuable marker to detect chronic rejection. Interactions of VSMCs and Fibro-/Myofibroblasts with ED-A(+) Fn and B(+) Tn-C might functionally contribute to the development of chronic cardiac rejection.
  Histochemie 10/2010; 134(5):503-17. · 2.59 Impact Factor
• Source

  Available from: PubMed Central

  Article: Epidermal growth factor receptor kinase domain mutations are rare in salivary gland carcinomas.

  R Dahse, O Driemel, S Schwarz, J Dahse, K Kromeyer-Hauschild, A Berndt, H Kosmehl
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  ABSTRACT: Activating mutations within the epidermal growth factor (EGFR) tyrosine kinase domain identify non-small cell lung cancer patients with improved clinical response to tyrosine kinase inhibitor therapy. Recently, we identified two EGFR mutations in a cohort of 25 salivary gland carcinomas (SGCs) by screening the tumour samples for the both most common hotspot mutations in exons 19 and 21 by allele-specific PCR. Here, we present a comprehensive sequencing analysis of the entire critical EGFR tyrosine kinase domain in 65 SGC of the main histopathological types. We found EGFR mutations in the tyrosine kinase domain to be a rare event in SGCs. No additional mutations other than the two known exon 19 deletions (c.2235_2249del15) in a mucoepidermoid carcinoma and an adenoid cystic carcinoma have been detected. Other putative predictive markers for EGFR-targeted therapy in SGCs might be relevant and should be investigated.
  British Journal of Cancer 02/2009; 100(4):623-5. · 5.04 Impact Factor
• Article: High-molecular tenascin-C as an indicator of atypical cells in oral brush biopsies.

  O Driemel, R Dahse, A Berndt, H Pistner, S G Hakim, L Zardi, T E Reichert, H Kosmehl
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  ABSTRACT: Tumour-invasion like wound healing is characterised by the formation of an extracellular matrix with a high tenascin-C content. The tenascin-C molecule undergoes alternative splicing. Analysis using antibody BC2 indicates that especially the high-molecular tenascin-C (hm tn-C) variants are typically tumour-associated, while distribution in normal tissue is restrictive. This study investigated whether hm tn-C is a suitable indicator of atypical cells with invasive potential in oral brush biopsies. One hundred fifty nine consecutive oral brush biopsies with histopathological diagnoses were analysed for the identification of atypical cells. A standardised haematoxylin and eosin staining plus standardised immunocytochemistry using the monoclonal anti-hm tn-C antibody was performed. The bound hm tn-C antibodies were detected with the streptavidine/alkaline phosphatase technique in the autostainer. Conventional cytology produced four false-positives when identifying atypical cells in brush biopsies of inflammatory/benign hyperproliferative mucosa (specificity 96%), while 10 in 52 carcinomas and three of eight recurrences were not identified (sensitivity 78%). Ten of these 13 non-identified tumours could be marked when adding the hm tn-C assay (increasing specificity to 99%). Combining the two assays also reduced the false-positive outcomes from four to one (increasing sensitivity to 95%). The positive and negative predictive values were 92 and 88% for conventional cytology vs 98 and 97% for the dual assay. (1) A 95%-sensitivity proves hm tn-C assisted conventional cytology to be a suitable means of identifying atypical cells in oral brush biopsies. (2) The positive (98%) and negative (97%) predictive values obtained approximate hm tn-C assisted conventional cytology to laminin-5 (100/97%).
  Clinical Oral Investigations 04/2007; 11(1):93-9. · 2.36 Impact Factor
• Article: [Clinical and immunohistochemical findings of intra- and extraoral angiosarcomas].

  Oliver Driemel, A Berndt, A Hartmann, U D Mueller-Richter, R Bauer, T E Reichert, H Kosmehl
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  ABSTRACT: A clinico-pathologic study of typical symptoms of intra- and extraoral angiosarcomas and clinical course under therapy is presented as well as an analysis of the immunohistochemical differential diagnosis of the tumour specific formed spaces. Four male patients aged 63-78 years suffered from angiosarcomas of the maxillary sinus, the bucca (two patients) and the alveolar ridge of the lower jaw. HISTOPATHOLOGY: For comparative analysis paraffin embedded tissue of the initial biopsies was available. The slides were stained with standardized H&E, PAS and Gömörri. For standardized immunohistochemistry following primary antibodies were applied: monoclonal antibodies to pancytoceratin clones AE1/AE3, alpha-smooth-muscle-actin clone 1A4, CD31 clone JC/70A, factor-VIII-related antigen clone F/86, Fli-1 (polyclonal, Zymed, USA), tenascin-C: BC4 (Prof. L. Zardi), oncofetal glucosylated fibronectin clone FDC6 (ACCR), laminin-5: D4B5. Detection using AP-ChemMate and Autostainer (Dako, Denmark). While the benign appearance of the lesions resulted primarily in wrong diagnoses the histopathologic examination of the biopsies revealed the characteristic pattern of angiosarcomas. Wide surgical excision, radiotherapy and/or antiangiogenic chemotherapy could not prevent tumour progression and death within two and a half years after primary diagnosis. All angiosarcomas reacted partially positive for factor-VIII-related antigen and CD31. The tumour associated structural defect of vascular lamina with partial loss of pericytes/vascular smooth muscle cells was identified immunohistochemically by alpha-smooth-muscle-actin and for the first time by tenascin-C. (1.) The variable presentation and the benign appearance of oral and perioral angiosarcomas may often delay diagnosis. Oral and perioral angiosarcomas show poor prognosis despite of multimodal therapy. (2.) Cytoceratin and laminin-5-positivity as typical epithelial antigens don't exclude angiosarcoma. Factor-VIII-related antigen, CD31 as well as Fli-1 identify angiosarcoma. (3.) alpha-smooth-muscle-actin and the loss of the tenascin-C-matrix indicate immunohistochemically the characteristic sarcomatous defect of differentiation.
  Mund- Kiefer- und Gesichtschirurgie 08/2006; 10(4):239-47.
• Article: [Bidirectional and unidirectional distraction of defects of the alveolar process comparative clinical study].

  P Schleier, H G Siebert, Ch Wolf, A Berndt, D Schumann
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  ABSTRACT: The purpose of the retrospective study was to compare bidirectional distraction osteogenesis with the currently used unidirectional method of alveolar ridge distraction with regard to bone height attained and complications. Overall 21 patients were treated by distraction osteogenesis for localized defects of the alveolar ridge. Vertical augmentation of the mandible and maxilla was performed using 10 unidirectional (group A) and 12 bidirectional (group B) devices. The effect of therapy was evaluated by height of bone gain and observed complications. The average gain of vertical bone height was approximately 6 mm. No statistically significant differences occurred between the two treatment groups (p=0.09). For the entire study two complications were observed: beside breakage of a distractor device (unidirectional distraction) an infection during the retention time (bidirectional distraction) developed. It could be shown that osteodistraction is a potentially valuable therapy for the correction of alveolar defects. We observed complications in both groups. No statistical differences were noted in regard to gained bone height and complications between the two groups.
  Mund- Kiefer- und Gesichtschirurgie 04/2006; 10(2):94-100.
• Article: [Simultaneous analysis of t(X;18) by FISH- und SYT/SSX-RT-PCR in synovial sarcoma].

  K Katenkamp, P Richter, T Slatosch, D Katenkamp, A Berndt
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  ABSTRACT: Synovial sarcoma diagnosis and differential diagnostic distinction from other spindle cell sarcomas may be difficult. In these cases the detection of the t(X;18) translocation by FISH and RT-PCR is diagnostically extremely helpful. This study was aimed at the question whether or not simultaneous use of both methods is required for evidence of t(X;18) translocation.Paraffin-embedded tumour specimens from 53 patients were included in the study which were considered to be possible synovial sarcomas on the basis of histological aspect and immunohistochemical profile. Detection of t(X;18) was performed using FISH and RT-PCR simultaneously. Nuclei and amplifiable RNA could be isolated from 39 of the 53 included cases (75%). In 72% of these 39 cases FISH and RT-PCR showed identical negative or positive results. The remainder of the cases (28%) showed either a typical PCR product or a positive FISH signal.In conclusions FISH could be confirmed by typical PCR products and is therefore qualified as an internal quality control. Nevertheless tumour biological and methodical reasons have an important influence on both methods. Consequently in difficult cases simultaneous FISH and RT-PCR analysis is necessary for a clear evidence of t(X;18) translocation.
  Der Pathologe 04/2005; 26(2):111-6. · 0.67 Impact Factor
• Source

  Available from: Luciano Zardi

  Article: Expression of fibronectin splice variants and oncofetal glycosylated fibronectin in the synovial membranes of patients with rheumatoid arthritis and osteoarthritis.

  J Kriegsmann, A Berndt, T Hansen, L Borsi, L Zardi, R Bräuer, P K Petrow, M Otto, C J Kirkpatrick, S Gay, H Kosmehl
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  ABSTRACT: The aim of this study was to define and compare the expression of fibronectin (Fn) isoforms in synovial tissue of patients with rheumatoid arthritis (RA) and osteoarthritis (OA). Using monoclonal antibodies specific for total Fn, extra domain (ED)-A Fn, ED-B Fn, and oncofetal glycosylated Fn, we studied the expression of the Fn isoforms in synovium. Furthermore, in situ hybridization for the detection of ED-B Fn mRNA including a double labeling technique for the detection of cell type was applied. Strong expression of total Fn, ED-A Fn, oncofetal glycosylated Fn and, to a lesser extent, ED-B Fn could be demonstrated in the synovial lining layer in both RA and OA. Stromal and vessel expression of Fn isoforms was more prominent in RA tissue. Pannus tissue showed strong labeling with ED-B Fn. The expression of alternatively spliced isoforms of Fn is associated with tissue remodeling and, as a partial process of this phenomenon, with neovascularization rather than underlying disease, X-ray status, or parameters of acute inflammation. In the lining layer, Fn expression correlates with hyperplasia associated with cell recruitment but not with proliferative status. Most remarkably, the expression of ED-B Fn in pannus tissue seems to be associated with the invasive phenotype described in RA tissue.
  Rheumatology International 02/2004; 24(1):25-33. · 1.88 Impact Factor
• Article: Influences of naturally occurring and experimentally induced porcine pneumonia on blood parameters.

  G Müller, H Köhler, R Diller, A Rassbach, A Berndt, D Schimmel
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  ABSTRACT: It had been the objective of the studies described to establish local and systemic changes by naturally occurring pneumonia or pneumonia experimentally induced by Pasteurella multocida and Haemophilus parasuis in swine. Acute and chronic pneumonia was found to alter the cytokine level of lung lavage fluid and affect the composition and function of blood cells, especially with regard to phagocytosis, radical formation and cell surface receptors. Interleukin-6 levels in blood plasma rose 24h after experimental intrabronchial infection. The influences of the changes on growth and meat quality are discussed.
  Research in Veterinary Science 03/2003; 74(1):23-30. · 1.65 Impact Factor
• Article: Effects of various applications of lipopolysaccharides on blood parameters of pigs.

  G Müller, G Steinbach, A Berndt, H Köhler
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  ABSTRACT: In five experiments, lipopolysaccharides (LPS) of Escherichia coli O26:B6 and O111:B4 were applied intravenously, intramuscularly, subcutaneously or intrabronchially in doses of 5000-15,000 U/kg body mass to a total of 47 weaner pigs and compared with the application of sodium chloride. Different parameters of blood cells were investigated, including cell numbers, in vivo interleukin secretion, radical formation, phagocytosis capacity and IL-6 as well as TNFalpha formation ex vivo. Non-specific effects and dependencies on the type of application and LPS dose are discussed.
  Journal of Veterinary Medicine Series B 12/2002; 49(9):429-37. · 1.48 Impact Factor
• Article: Laser capture microdissection in 2-D co-culture models as a tool to study tumor-stroma interactions.

  R Dahse, A Berndt, K M Haas, P Hyckel, F D Böhmer, U Clauseen, H Kosmehl
  BioTechniques 10/2002; 33(3):474-5. · 2.67 Impact Factor
• Article: Cytokine mRNA expression in experimental porcine pneumonia.

  A Berndt, M Heller, H Kosmehl
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  ABSTRACT: A porcine Pasteurella multocida (P. m.) infection model was established to study the spatial distribution of cytokine mRNA-expressing cells in lung tissue during acute pneumonia. The mRNA detection was performed by non-radioactive, formamide-free in situ hybridization (ISH) using oligonucleotides against the porcine interleukins (IL): IL-1 beta, IL-2, IL-4, IL-6, IL-8, TNF alpha and TGF beta. Cytokine mRNA-expressing macrophages were demonstrated by a double staining procedure combining immunohistochemistry (IH) using the primary antibody 2G6 with IL-1 beta, IL-6 and TGF beta ISH. With the exception of some stained TNF alpha-expressing cells, no IL mRNA was detectable in the lung of unaffected animals. The experimental P. m. pneumonia was characterized by a predominant, exudative and an additional proliferative interstitial component as well as abscess formation in the lung. Many cells of the region between the abscess membrane and the affected lung area showed high IL-6, IL-1 beta, IL-4 as well as TGF beta and few cells low IL-8 mRNA expression with characteristic distribution patterns. The ISH/IH double staining procedure revealed that at least some of the IL-6 or TGF beta-producing cells belonged to the 2G6-positive macrophages.
  DTW. Deutsche tierärztliche Wochenschrift 05/2002; 109(4):205-9. · 0.41 Impact Factor
• Article: Enhancement of the antitumor activity of interleukin-12 by targeted delivery to neovasculature.

  C Halin, S Rondini, F Nilsson, A Berndt, H Kosmehl, L Zardi, D Neri
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  ABSTRACT: Interleukin-12 (IL-12) is a heterodimeric cytokine with potent immunostimulatory activity and anti-angiogenic properties. Its clinical applications are limited, however, by severe side-effects. Here we report that an IL-12 fusion protein, consisting of IL-12 fused to a human antibody fragment specific to the oncofetal ED-B domain of fibronectin, markedly enhances the antitumor activity of this cytokine, as demonstrated in a mouse lung-metastasis model and in two models of mice bearing different aggressive murine tumors. The residual small tumor masses seen in the treated mice were infiltrated with lymphocytes, macrophages, and natural killer cells and had elevated interferon gamma (IFN-gamma). These results are of therapeutic relevance as the ED-B domain of fibronectin, a naturally occurring marker of angiogenesis identical in mouse and man, is expressed in the majority of aggressive solid tumors but is not detectable in normal vessels and tissues.
  Nature Biotechnology 04/2002; 20(3):264-9. · 23.27 Impact Factor
• Article: A comparative quantitative analysis of laminin-5 in the basement membrane of normal, hyperplastic, and malignant oral mucosa by confocal immunofluorescence imaging.

  K M Haas, A Berndt, K J Stiller, P Hyckel, H Kosmehl
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  ABSTRACT: Laminin-5 (Ln-5) is a heterotrimeric basement membrane (BM) molecule (alpha3beta3gamma2). It is a principal protein constituent of the anchoring filaments, which connect the BM with the hemidesmosomes of the basal keratinocytes and possess a crucial function in keratinocyte adhesion. Confocal immunofluorescence imaging is introduced for a quantitative evaluation of the Ln-5 content in the BM of oral squamous epithelium. The BM of normal oral mucosa was used as a reference (100%) for comparative analysis and showed a nearly uniform Ln-5 immunofluorescence intensity (99-100%). In all hyperplastic lesions of oral mucosa, the Ln-5 immunofluorescence intensity was increased (107-141%). The increased Ln-5 content in the BM of hyperplastic lesions suggests an increased keratinocyte-BM adhesion, possibly resulting in a higher stability of the oral mucosa. In contrast, in the oral squamous cell carcinoma (OSCC) invasive front, the remaining BM segments were characterized by a decrease in Ln-5 immunofluorescence intensity (35-74%). A stronger decrease of Ln-5-linked kerationocyte-BM adhesion correlates with a higher tumor grade. Because in central areas of carcinoma BM segments with a normal Ln-5 content could be demonstrated, the fundamental Ln-5 diminution in BM segments of the invasive front should be considered as an invasion-associated phenomenon.
  Journal of Histochemistry and Cytochemistry 11/2001; 49(10):1261-8. · 2.72 Impact Factor
• Article: Fibrillary co-deposition of laminin-5 and large unspliced tenascin-C in the invasive front of oral squamous cell carcinoma in vivo and in vitro.

  A Berndt, L Borsi, P Hyckel, H Kosmehl
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  ABSTRACT: Invasion of oral squamous cell carcinoma (OSCC) is associated with laminin-5 (Ln-5) synthesis, focal Ln-5 loss from the basement membrane (BM), and Ln-5 depositions in the stroma beneath invading carcinoma cell complexes. The study is focused on the laminin-5 matrix reorganisation within the stroma of the OSCC invasive front outside the basement membrane region as well as in OSCC-fibroblast co-culture in relation to unspliced tenascin-C (Tn-CL) and ED-B+ fibronectin (ED-B+ fn) using confocal laser scanning microscopy. In vivo, Ln-5 was demonstrated as fibrillary deposition in the invasive front. It was co-localised to Tn-CL. In pure OSCC cultures, Ln-5 was synthesised and deposited as a spot-like matrix. Fibrillary structures were not found. In contrast, in the OSCC-fibroblast co-culture, a fibrillary Ln-5 matrix organisation was revealed within the interface of OSCC cell-fibroblast complexes exclusively in co-distribution with Tn-CL and ED-B+ fn. At least in vitro, a carcinoma cell-stroma fibroblast interaction is indispensable for fibrillary Ln-5/Tn-CL matrix organisation. Behind the parallels to the initial basement membrane formation in organotypic cultures, the fibrillary multiprotein complexes at the OSCC cell-fibroblast interface are suggested as provisional basement membrane fragments with a possible supportive role for invasive tumour behaviour.
  Journal of Cancer Research and Clinical Oncology 06/2001; 127(5):286-92. · 2.56 Impact Factor
• Article: Elevated activity and expression of Src-family kinases in human breast carcinoma tissue versus matched non-tumor tissue.

  D Reissig, J Clement, J Sänger, A Berndt, H Kosmehl, F D Böhmer
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  ABSTRACT: Src-family kinase expression was measured in 52 human mammary tumor (T) specimens compared with non-tumor (NT) tissue from the same patient by enzymatic assays employing a Src-kinase family-specific peptide substrate and by immunoblotting with an antibody recognizing the Src-family kinases Src, Fyn, and Yes. In the T specimens, the mean enzymatic activity was moderately elevated (T: 160 fmol ATP min-1 mg-1; NT: 115 fmol ATP min-1 mg-1) with 25 tumor samples having higher activity than the corresponding NT tissue, 17 having lower activity, and no activity detectable in ten T/NT pairs. Immunoblotting revealed clearly elevated expression in 25 tumor tissues and no differences or expression below the detection limit in the remaining T/NT pairs. The data are in agreement with a possible role of Src-family kinases for the biology of mammary carcinoma.
  Journal of Cancer Research and Clinical Oncology 05/2001; 127(4):226-30. · 2.56 Impact Factor
• Article: [Tumors of the face in organ transplant patients].

  P Hyckel, A Berndt, P Wutzler, H Kosmehl
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  ABSTRACT: BACKGROUND: The greatly enhanced risk of developing pre-cancerous lesions, basal cell carcinomas, and squamous cell carcinomas in organ transplant recipients is demonstrated on the basis of three of our own cases. DISCUSSION: Immunosuppression is discussed as the primary reason for enhanced tumour incidence and the occurrence of multiple synchronic and metachronic tumours after organ transplantation. UV exposition and oncogenic viruses must be taken into account as further factors for tumour disposition. More aggressive tumour behaviour has to be expected. In consequence, a focused clinical monitoring and a stringent therapy of the skin tumours is absolutely necessary.
  Mund- Kiefer- und Gesichtschirurgie 04/2001; 5(2):94-7.
• Article: [Experimental 5-aminolevulinic acid-induced photodynamic therapy (ALA-PDT) of oral carcinomas. Procedures in treatment of solid tumors and elucidation of cell death].

  P Schleier, A Berndt, R Dahse, W Zenk, P Hyckel, H Kosmehl
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  ABSTRACT: Of our own patients suffering from oral squamous cell carcinoma (OSCC), 96% possessed a 5-aminolevulinic acid (ALA)-induced tumor fluorescence. Consequently, the ALA-induced fluorescence of OSCC is suggested as an ideal tool for selective photodynamic therapy (PDT). The aim of the study was to demonstrate selective tumor damage and to analyze the cell death mode (apoptosis vs. necrosis) of OSCC cells in cell culture and in solid, deeply invasive xenotransplants in immunodeficient nude mice using intratumoral laser illumination. For ALA-PDT, laser light (635 nm, 0.75 W, 10 min, cooled application system) was used intratumorally as well as in cell culture. The therapeutic response was controlled by histology and immunohistochemistry (Ki-67 index). The apoptosis was evaluated by the TUNEL method and in vitro by flow cytometry. Mutations in the apoptosis-controlling p53 gene were investigated by direct genomic sequencing. 1. Although all OSCC exhibited an ALA-induced fluorescence in vivo, the evaluation of the cell lines showed differences in intensity of the ALA-induced fluorescence. This points to a different sensitivity of OSCC for ALA-PDT. 2. The use of a cooled laser light application system allowed intratumoral radiation and treatment of deeply invasive OSCC regions. 3. The cytotoxic effect of ALA-PDT in OSCC is evidenced by a diminution of proliferative activity and necrosis but not by apoptosis. 4. Functional mutations within the p53 gene were considered a possible reason for the absence of apoptosis induction by ALA-PDT.
  Mund- Kiefer- und Gesichtschirurgie 04/2001; 5(2):98-104.