Biomedical subjects

K Götte

Publications and source records attributed to K Götte.

31 records · Page 2Linked to original sources

PubMed2000

Expression of 92-kDa type IV collagenase correlates with angiogenic markers and poor survival in head and neck squamous cell carcinoma.

MMP-9, which degrades extracellular matrix, is believed to play a crucial role in tumor invasion and metastasis. Angiogenesis is also perceived as an important step in tumor growth and metastasis. The aim of this study was to investigate the expression of MMP-9 in tumor samples of HNSCC patients and to study a possible correlation to angiogenic markers. Cryostat sections of 52 HNSCC tumors were immunostained for MMP-9, bFGF and VEGF using a standard streptavidin-biotin complex procedure for light microscopic investigation. Microvessel density (MVD) was determined by staining of endothelial cells immunohistochemically using anti-vWF monoclonal antibody. MMP-9 positive staining was detected in 27/52 (52%) of the tumors. MMP-9 immunoreactivity did not correlate with the main clinicopathological characteristics of the patients (localisation, T-stage, N-stage, histological grading), but correlated with worse survival of the patients. MMP-9 negative tumors showed a significant lower mean MVD per microscopic field than MMP-9 positive tumors (p<0. 001). There was a significant association of MMP-9 and VEGF expression (p<0.05). The presence of MMP-9 in HNSCC cancer and the positive correlation with MVD and VEGF expression supports the theory that MMP-9 functions as a regulator of tumor angiogenesis supporting endothelial cell invasion. MMP-9 and VEGF might act co-operatively in the process of neovascularization in human head and neck cancer.

Adult↗

PubMed1999

Hereditary hemorrhagic telangiectasias: a challenge for the clinician.

Hereditary hemorrhagic telangiectasia (Osler-Weber-Rendu disease) remains a challenge for all clinicians, as in about 80% of cases nasal bleeding is the first manifestation of this disease, which is characterized by a clinical triad of multiple telangiectasias, recurrent hemorrhages and familial occurrence. Although in the last few years there has been diagnostic and therapeutic progress, a cure for this rarely life-threatening but often burdening and handicapping disease is still not possible. We have reviewed head and neck presentations, diagnostic and therapeutic features, as well as new insights into the molecular genetics of the disease and local treatment now available.

Diagnosis, Differential↗

PubMed1999

Congenital nasal hemangiopericytoma: intrauterine, intraoperative, and histologic findings.

Hemangiopericytoma is a rare tumor of mesenchymal origin. To date, 91 cases of nasal or paranasal hemangiopericytoma and 59 congenital hemangiopericytomas have been reported in the literature. A congenital hemangiopericytoma arising from the nasal cavity and skull base has not yet been described. We report a case of a male newborn with a highly vascular nasal tumor diagnosed by in utero sonography with three-dimensional surface reconstruction. The tumor extended to the right anterior skull base, the right nasal cavity, and the right side of the nasal pyramid. A complete resection by neodymium:yttrium-aluminum-garnet-potassium titanyl phosphate ("Nd:YAG-KTP") laser was performed on the day of cesarean section at 33 weeks' gestation. The tumor was diagnosed as hemangiopericytoma by histologic and immunohistochemical findings. Postoperative nasal flow, feeding, and sight were unimpaired. At the 9-month follow-up, the infant remained free of disease.

Female↗

PubMed1998

[Argon plasma coagulation in treatment of hereditary hemorrhagic telangiectasia of the nasal mucosa].

Patients with hereditary hemorrhagic telangiectasia (M. Osler-Rendu-Weber disease) often suffer from recurrent epistaxis that poses considerable therapeutic problems. Dermoplasty, electrocoagulation, laser coagulation, iridium brachytherapy and systemic administration of estrogens have been proposed for treatment. Until recently argon plasma coagulation (APC) was not used in ENT surgery, but theoretical considerations render APC a promising therapeutic method for controlling nasal bleeding. Coagulation of tissue is limited to 1-2 mm of penetration and therefore risk of damage to adjacent tissue is low. Effects are best in tissues with high electric conductivity, especially for coagulating bleeding lesions and blood vessels. We have now treated four patients with telangiectasias in the nasal mucosa who had long histories of treatment for epistaxis. The patients were satisfied with the postoperative results and the frequency and intensity of bleeding were significantly reduced. Initial clinical experiences show that APC is a useful alternative for the treatment of bleeding telangiectasias in the nasal mucosa.

Adult↗

PubMed1998

Pex19p, a farnesylated protein essential for peroxisome biogenesis.

We report the identification and molecular characterization of Pex19p, an oleic acid-inducible, farnesylated protein of 39.7 kDa that is essential for peroxisome biogenesis in Saccharomyces cerevisiae. Cells lacking Pex19p are characterized by the absence of morphologically detectable peroxisomes and mislocalization of peroxisomal matrix proteins to the cytosol. The human HK33 gene product was identified as the putative human ortholog of Pex19p. Evidence is provided that farnesylation of Pex19p takes place at the cysteine of the C-terminal CKQQ amino acid sequence. Farnesylation of Pex19p was shown to be essential for the proper function of the protein in peroxisome biogenesis. Pex19p was shown to interact with Pex3p in vivo, and this interaction required farnesylation of Pex19p.

Amino Acid Sequence↗

PubMed1997

[The treatment of juvenile laryngeal papillomatosis with argon plasma coagulation].

HISTORY AND CLINICAL FINDINGS: At 3 years of age a girl known for one year to have progressive juvenile laryngeal papillomatosis with involvement of the lower respiratory tract was seen by her general practitioner because of increasing hoarseness. As about 20 sessions of CO2-laser treatment and adjuvant administration of interferon-alpha had failed to prevent increasing glottal stenosis and spread of the tracheal involvement, a tracheostomy had to be performed. Removal of the papilloma became progressively more difficult and at the age of 6 years she was admitted for further treatment. INVESTIGATIONS: She had marked inspiratory and expiratory stridor. Results of laboratory tests were unremarkable. Examination of the respiratory tract with a flexible endoscope revealed obstruction of the tracheal lumen by the papilloma. TREATMENT AND COURSE: The papilloma was removed by argon plasma coagulation (APC) under general anaesthesia during intermittent apnoeic phases. After four treatment sessions no papilloma could be seen endoscopically. There were no side effects or complications. The interval between treatments has become progressively longer. Further removal of papilloma is only rarely necessary nowadays. CONCLUSION: APC via a flexible endoscope is a promising method in the treatment of juvenile laryngeal papillomatosis involving the lower respiratory tract. It achieves precise, circumscribed tissue penetration without carbonisation or steaming-up, while bleeding can be controlled.

Child, Preschool↗

PubMed1997

Treatment of recurrent respiratory papillomatosis with argon plasma coagulation.

Extension of recurrent respiratory papillomatosis (RRP) to the lower airway in children is life-threatening and an extremely difficult condition to treat. We present the case of a seven-year-old girl with progressive RRP since the age of two. Repeated CO2 laser treatment and interferon-alpha treatment could not prevent tracheotomy and spread to the trachea. We used argon plasma coagulation (APC) with flexible endoscopy for the first time for the treatment of RRP. APC gives a controlled limited penetration into the tissue and good control of bleeding. There is no carbonization or vaporization which makes it a suitable method for the treatment of lower airway RRP. After a few treatments with APC, we gained very good control of the disease with no side-effects or complications. The described application of APC seems to be a promising way to treat lower airway RRP.

Child, Preschool↗

PubMed1993

Two complementary approaches to study peroxisome biogenesis in Saccharomyces cerevisiae: forward and reversed genetics.

In order to investigate the mechanisms of peroxisome biogenesis and to identify components of the peroxisomal import machinery we studied these processes in the yeast Saccharomyces cerevisiae. The forward genetic approach has led to pas-mutants (peroxisomal assembly) which fall into 12 complementation groups and allowed to identify 10 of the corresponding wild-type PAS genes (PAS 1-7, 9, 11 and 12). Recent sequence analysis data of some of these genes are beginning to provide first hints as to the possible function of their gene products. The PAS genes and their corresponding mutants are presently used to address some important questions of peroxisomal biogenesis. Reversed genetics has been started as a complementary approach to characterize especially the function of peroxisomal membrane proteins. For this purpose we describe a technique to isolate highly purified peroxisomes. This led to the identification of 21 polypeptides as constituents of this organelle. Some of them are presently sequenced.

Adenosine Triphosphatases↗

PubMedDate not supplied

Fhit expression is absent or reduced in a subset of primary head and neck cancer.

BACKGROUND: The inactivation of the FHIT gene at 3p14.2 by various mechanisms might be of importance in head and neck squamous cell carcinoma (HNSCC). Most reports are based on DNA and RNA findings of intragenic deletions and abnormal transcripts. MATERIAL AND METHODS: To study the protein expression of this putative tumour suppressor gene, we analysed 48 HNSCCs by immunohistochemistry using a polyclonal antibody (ZR44). The results were compared with mutation analysis, clinical data and loss of heterozygosity (LOH) data at 3p14.2. RESULTS: Complete absence of Fhit expression was detected in 8 out of 48 of tumours (17%) and 3 tumours (6%) showed heterogenous staining. The overall frequency of LOH for microsatellite D3S1234 was 64% and 5/7 of Fhit negative tumours exhibited LOH. CONCLUSION: Our findings provide further evidence that FHIT is inactivated in a subtype of HNSCC; however, the incidence of lack of Fhit expression compared to the high frequency of LOH on chromosome 3p supports the notion of additional tumour suppressor genes at 3p14.

Acid Anhydride Hydrolases↗

PubMedDate not supplied

Serum levels of matrix metalloproteinase-2 and -9 in patients with head and neck squamous cell carcinoma.

BACKGROUND: Matrix Metalloproteinases (MMPs) have been implicated as playing an important role in cancer invasion and metastasis. MMPs have been identified in a wide variety of malignancies including head and neck squamous cell carcinomas (HNSCC). MATERIAL AND METHODS: We investigated the circulating level of MMP-2 (gelatinase A or 72-kD type IV collagenase) and MMP-9 (gelatinase B or 92-kD type IV collagenase) in sera from patients with various head and neck squamous cell carcinomas (n = 86) as well as from healthy normal controls (n = 47). Serum MMP concentrations were determined as serum immunoreactivity by using a quantitative sandwich enzyme immunoassay technique. For statistical analysis, the t-test and Kruskal-Wallis test were performed. RESULTS: The majority of the patients with HNSCC were found to have high concentrations of serum MMP-9. The levels of MMP-9 in the sera of patients with cancer ranged from 39 to 1547 ng/ml (mean, 417 ng/ml). In contrast, the MMP-9 serum levels in 47 healthy individuals ranged from 30 to 537 ng/ml (mean, 189 ng/ml), MMP-9 serum concentration being significantly higher in HNSCC patients (p = 0.001). MMP-9 serum concentrations of patients with advanced stage HNSCC were significantly higher (p = 0.0449) compared to patients with early stage cancer. No significant difference of MMP-2 serum levels was seen when comparing HNSCC patients and normal controls. CONCLUSION: The present data indicate that the elevation of serum levels of MMP-9, but not MMP-2, may be a useful marker for clinical monitoring of HNSCC patients.

Adult↗

PubMedDate not supplied

Inverse correlation of apoptotic and angiogenic markers in squamous cell carcinoma of the head and neck.

Angiogenesis is essential for tumour growth and metastasis. The induction of tumour vascularization is mediated by the release of angiogenic peptides. Among these factors, basic fibroblast growth factor (bFGF), vascular endothelial growth factor (VEGF) and matrix metalloproteinase-9 (MMP-9) are thought to be the most important. Previous experimental studies indicate that the process of apoptosis, the programme of cell death, may be related to angiogenesis in head and neck carcinogenesis. Therefore, cryostat sections of 49 head and neck squamous cell carcinomas (HNSCC) were investigated immunohistochemically for pro-apoptotic factors caspase-3 and Fas ligand (FasL) using a standard streptavidin-biotin complex procedure. Expression of bFGF, VEGF and MMP-9 served as angiogenic markers. Additionally, intratumoral microvascular density (MVD) was counted by immunostaining of endothelial cells using anti-vWF antibody. Comparing the expression of apoptotic and angiogenic factors, a statistically significant inverse correlation of caspase-3 expression and VEGF and MMP-9 expression was found. Concerning FasL, the correlation of its expression with expression of VEGF, bFGF and MMP-9 was inversely correlated. With respect to vWF-immunostaining, statistical analysis gave a clear inverse correlation between the tumour vascularity and the expression of FasL (p = 0.0008) and caspase-3 (p = 0.0068). Our results suggest that HNSCC tumour angiogenesis contributes to a reduction of apoptosis in tumour cells. This may be explained by the activation of pro-apoptotic factors caused by hypoxia.

Adult↗

PubMedDate not supplied

Immunocytochemical localization of basic fibroblast growth factor in squamous cell carcinomas of the head and neck.

Angiogenesis is crucial for tumour growth and formation of metastasis. Basic fibroblast growth factor (bFGF) is known to have potent angiogenic activity and has been identified in a wide variety of malignancies including head and neck squamous cell carcinomas (HNSCC). Clarification of its localization in HNSCC is important for the understanding of angiogenesis. Cryosiat sections of 27 HNSCC were immunostained for bFGF using a standard streptavidin-biotin complex procedure. Western blot analysis revealed three immunoreactive bFGF isoforms of 18, 22 and 24 kDa. Immunohistochemical and -cytochemical localization of bFGF was studied at light and electron microscopic levels. bFGF was mainly localized within the focal tumoral areas rather than in the tumour stroma. On a subcellular level, the ultrastructural investigation showed electron-dense bFGF localization in the cytosol of the carcinoma cells, but bFGF labelling within the nuclei of HNSCC cancer cells was one prominent finding of this study. In conclusion, the presence of bFGF isoforms in most of the cancer cells supports the theory of a direct paracrine mechanism of bFGF from cancer cells on tumour angiogenesis. The nuclear localization of bFGF in the HNSCC cells supports its activity as a transcriptional factor.

Biotin↗

PubMedDate not supplied

Genetic discordance between primary tumours and metastases of head and neck cancer detected by microsatellite analysis.

Very little is known about possible intra-tumoural genetic heterogeneity between primary tumours and lymph node metastases in head and neck squamous cell carcinoma (HNSCC). To investigate this phenomenon, we analysed 96 micro-dissected tumour samples for allelic imbalance at four of the most frequently altered chromosomal locations in HNSCC (3p14.2; 9p21; 11q23.3; 17p13.1) using microsatellite markers. From 23 patients, matched pairs of primary tumour and lymph node metastasis were analysed. Discordance in the allelic distribution was identified in 8 cases (35%). With one exception, the metastasis contained a more balanced allelic status than the primary tumour. In contrast, in a group of 25 tumours with two anatomically different samples from the primary tumour site, discordance was identified in only 3 tumours (13%). These results are compatible with the dissemination of subclones from the primary tumour site with a more balanced allelotype in the metastasis. In our opinion, several scenarios could explain this phenomenon. From a clinical point of view, genetic discordance between the metastasis and the primary tumour must be taken into consideration when establishing molecular biologic markers for choice of therapy and prognosis in head and neck cancer.

Allelic Imbalance↗