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Biomedical subjects

A Tannapfel

Publications and source records attributed to A Tannapfel.

At least 127 records · Page 7Linked to original sources

The prediction of lymph node metastases in colorectal cancer by expression of the nucleoside diphosphate kinase/nm23-H1 and histopathological variables.

OBJECTIVE: To ascertain the risk of locoregional lymph node metastases from colorectal cancer, we compared microscopic pathological characteristics of the primary tumor with the expression of the nm23-H1 protein. METHODS: The nm23-H1 expression of 100 colorectal carcinomas and corresponding non-neoplastic mucosa was analyzed immunohistochemically at the time of primary curative surgery (R0 resection). Conventional histopathological factors (depth of infiltration, grade of differentiation, invasion of lymph vessels or veins) that are proven indicators for metastatic involvement of locoregional lymph nodes were examined in all cases. RESULTS: Of 45 tumors with lymph node metastases, 42 (93%) had a low nm23-H1 expression whereas only 35 (78%) were of high-risk histology (G3, G4, or lymphatic invasion). Therefore, nm23-H1 expression within the primary tumor indicated the lymph node status with a sensitivity of 93% and a negative predictive value of 92%. The classic pathohistological factors (high risk vs low risk) had a sensitivity of 78% and a negative predictive value of 77%, respectively. CONCLUSION: Reduced expression of nm23-H1 within primary colorectal carcinomas could serve as an additional independent marker in estimating the nodal metastatic potential of these tumors.

Antigens, Neoplasm↗

Prognostic value of ploidy and proliferation markers in renal cell carcinoma.

BACKGROUND: The prognosis for patients with renal cell carcinoma depends mainly on pathological stage and grade of the tumor at the time of surgery. Cellular proliferation may prove to be another measure for predicting biologic aggressiveness and, therefore, the prognosis. METHODS: The authors compared four different methods to assess proliferation in a series of 87 curatively resected (R0) renal cell carcinomas: flow cytometry analysis (FCM), silver-stained nucleolar organizer regions (AgNOR), and immunohistochemical assessment of the MIB-1 (Ki-67) antigen, and proliferating cell nuclear antigen (PCNA). The results obtained were compared with pathologic stage (according to the International Union Against Cancer [UICC]) and grade with disease-related survival rate; finally, we assessed whether the methods led to similar results. RESULTS: In each carcinoma examined, we could demonstrate MIB-1, PCNA, and AgNOR dots in varied proportions. Statistical correlations were seen between the tumor grade, the rate of nuclear positivity for MIB-1 and PCNA, and the number of AgNOR dots. Additionally, the MIB-1 index was significantly higher in more advanced tumor stages. A good correlation between MIB-1 and AgNOR as well as for PCNA was found. In univariate survival analysis, tumor stage and grade, MIB-1 and PCNA index, and mean AgNOR number were related significantly to patient survival. On multivariate Cox disease-related survival analysis, stage of disease and MIB-1 were significant independent prognostic factors. Flow cytometry was not related to prognosis nor to other examined parameters. CONCLUSIONS: These results indicated that MIB-1 immunostaining is an additional prognostic parameter for patient outcome. MIB-1 and PCNA immunostaining, as well as AgNOR, demonstrated good correlations among themselves. We failed to establish flow cytometry as a method to predict proliferative capacity or prognosis in renal cell carcinoma patients.

Antigens, Nuclear↗

[The development of metastases and their classification].

PURPOSE: The process of metastasis has been elucidated by thorough morphological studies on resection specimens and new findings in the field of molecular biology in recent years. The successful surgical removal of distant metastases lead to the necessity of a detailed and precise classification system of distant metastases. PATIENTS AND METHODS: The new molecular findings as well as data obtained from morphological studies and the results of a international field study on behalf of the UICC lead to the proposed system presented here as a new classification system for metastases. RESULTS: A general classification of distant metastases of any primary tumor should separate 5 different categories: M1 for non-regional lymph node metastases only, M2 for liver metastases only, M3 for lung metastases only, M4 for bone metastases only and M5 for metastases in 2 or more of these organs or others. In case of liver metastases of colorectal carcinoma, 2 different classifications were proposed; a clinical classification based on locoregional tumor status, number of liver metastases and involved lobes and a post-surgical classification depending on locoregional tumor status and size of metastases removed surgically and assessed by the pathologist. CONCLUSION: More detailed knowledge of the metastatic process and success in surgical treatment makes a detailed and exact classification system for distant metastases essential. This should be used as a fundamental base for future therapeutical and prognostic studies.

Classification↗

Expression of c-erbB2 oncogene product in different tumours and its standardised evaluation.

In order to evaluate the reliability and reproducibility of the immunohistochemical demonstration of the c-erbB2 oncoprotein and define criteria for positivity assessment in paraffin-embedded material from different tumours, we examined immunohistochemically 79 gastric, 100 colorectal and 20 bladder carcinomas using 5 different c-erbB2 antibodies. To determine criteria for the evaluation of c-erbB2 positivity, the observed immunohistochemical staining was compared with the actual protein prevalence, determined by Western blot analysis of each tumour. The comparison of protein levels obtained from Western blot with corresponding immunohistochemistry revealed that positive staining can only be considered to be specific for c-erbB2 oncoprotein if: (i) there is a definite staining along the tumour cell membrane with no predominant immunoreactivity inside the tumour cell cytoplasm, (ii) the intensity of immunoreactivity is comparable with a positive standard (e.g. in this study breast carcinoma) and (iii) the surrounding normal, non-neoplastic tissue shows no immunoreactivity. The graduation of staining intensities did not correlate to the actual amount of protein detected in Western blots. This study stresses the importance of defined and controlled criteria for evaluation of c-erbB2 oncoprotein positivity in immunohistochemistry.

Blotting, Western↗

Expression of nm23-H1 predicts lymph node involvement in colorectal carcinoma.

PURPOSE: Reduced expression of the metastasis suppressor gene nm23-H1 has previously been correlated with high tumor metastatic potential and fatal clinical outcome in some tumors (e.g., breast). For colorectal carcinomas, the findings are equivocal. METHODS: We have used a monoclonal antibody against nm23-H1 to investigate the expression in colorectal carcinomas at the time of primary curative surgery (R0 resection) to assess if there was any relation between nm23-H1 expression and stage or histologic grade at the time of primary tumor removal. RESULTS: Of 100 colorectal carcinomas studied (Stages I, II, and III according UICC, all resected curatively), nm23-H1 immunoreactivity was weak in 41 (41 percent), moderate in 24 (24 percent), and strong in 35 (35 percent) cases. The grade of positivity against nm23-H1 was significantly lower in advanced stages of the disease (Stages II or III) (P < 0.001, chi-squared = 52.8). In tumors with low or weak immunoreactivity against nm23-H1, frequency of lymph node metastases was significantly higher compared with those with moderate or strong staining (P < 0.001; chi-squared = 50.58). Therefore, with a sensitivity of 93 percent and a specificity of 58 percent, low nm23-H1 immunoreactivity of the primary tumor, assessed at the time of surgery, is an indicator of the presence of lymph node metastases. CONCLUSIONS: Immunohisto-chemical evaluation of nm23-H1 in the primary tumor or in a biopsy is a useful predictor of stage of disease and presence of lymph node metastases in colorectal carcinomas and may have clinical significance, e.g., in predicting optimal therapeutic regimes.

Biomarkers, Tumor↗

Effect of hepatocyte growth factor on the expression of E- and P-cadherin in gastric carcinoma cell lines.

Hepatocyte growth factor (HGF), identical to scatter factor, (SF) is a secretory glycoprotein from fibroblasts which dissociates and increases the motility of various types of epithelial cells. After treatment of three gastric carcinoma cell lines (MKN-28, MKN-45 and TMK-1) with HGF (10 ng/ml), TMK-1 cells lost their tight cell to cell contact and showed marked scattering, while the two other cell lines remained unaffected. To learn about the underlying mechanism of the HGF induced scattering, we examined the expression of adhesion molecules and growth factor/receptor systems at the mRNA and protein level. The observed scattering of treated TMK-1 cells was associated with a reduction in the expression of E- and P-cadherin protein. The respective mRNA levels remained unchanged after HGF/SF treatment. In the two other cell lines, which showed no scattering, there were no changes in the expression of E- and P-cadherin. All other growth factors and their receptors examined (TGF-alpha, EGFR, c-met and c-erbB2) remained constant and were not affected by HGF treatment. The results suggest that HGF/SF may regulate cell adhesion in gastric carcinomas via E- and P-cadherin expression at the protein level.

Adenocarcinoma↗

Effect of hepatocyte growth factor (HGF)/scatter factor (SF) on cell adhesion in gastric cancer.

Hepatocyte Growth Factor (HGF)/Scatter Factor (SF) is a secretory glycoprotein from stromal fibroblasts which binds to the transmembrane c-met receptor. This receptor is expressed from a variety of tumors, including gastric carcinomas. To look for a possible paracrine loop between gastric cancer cells and their surrounding fibroblasts in gastric carcinoma, the effect of HGF/SF treatment on the morphology and the expression of cell adhesion molecules was examined. The cell line TMK-1, established from poorly differentiated gastric carcinoma, responded with scattering after HGF/SF treatment. We found that the observed morphological changes were accompanied with a reduced expression of E- and P-cadherin protein in these cells. In a cell line established from well differentiated gastric carcinoma, named MKN-28, neither scattering nor changes in cadherin expression could be detected. This results suggested, that HGF/SF is a regulator of cell adhesion via affecting E- and P-cadherin. Taking into account, that only cells from poorly differentiated gastric carcinoma cell lines responded in scattering after HGF/SF treatment, paracrine secreted HGF/SF may play an important role in the pathogenesis of these type of gastric carcinoma in vivo.

Adenocarcinoma↗

Ductal adenocarcinoma of the pancreas. Histopathological features and prognosis.

Between 1972 and 1987, curative surgical resection (RO) was performed in 81 patients with ductal adenocarcinoma of the pancreas. In this study, slides from surgical specimens were reviewed, and histopathological features of the carcinomas were retrospectively reevaluated. Tumor stage was the most important prognostic factor: In UICC stages I, II, and III, the median survival times were 13, 16, and 8 mo, respectively. Lymph node involvement and direct extension of the tumor into adjacent peripancreatic tissue, as well as invasion into peripancreatic organs were found to significantly influence survival. Tumor infiltration of the lymphatic vessels was present in 74% of the resected carcinomas and significantly correlated with survival time. There was no relationship between survival and tumor size; furthermore, histological grade of differentiation, age, and sex had no influence on prognosis.

Adenocarcinoma↗

Micro- and macrovesicular steatotic liver model for transplantation induced by ethanol and protein-deficient diet.

Steatotic liver grafts are associated with a high incidence of primary nonfunction and initial poor function. Due to the increasing number of liver transplant candidates, centers are inclined to accept marginal donors more frequently. For a lack of a reliable fatty liver model, preservation concepts for fatty livers have hardly been evaluated. Moreover, there is an ongoing debate on the relevance and impact of micro- versus macrovesicular steatotic organs. We therefore intended to establish a steatotic liver model in pigs comprising both micro- and macrovesicular steatotic livers. Five groups of pigs received daily 1 to 6 g ethanol/kg body weight and/or a protein-deficient diet for up to 72 days. Liver biopsy was carried out at days 24, 48, and 72. With an increasing amount and duration of ethanol intake, higher levels of microvesicular steatosis were induced. Ethanol and protein deficient diet resulted in more than 60% microvesicular steatosis after 72 days. Exclusively protein-deficient diet without ethanol induced macrovesicular steatosis of more than 70% after 72 days. For the first time, we established a porcine model of hepatic steatosis that comprises both histologic types of fatty liver: micro- and macrovesicular steatosis induced by ethanol and a protein-deficient diet. We would like to conclude that our model is particularly qualified to study new concepts of preservation for steatotic livers to improve on the posttransplant outcome.

Animals↗

[Long-term study of patients with coeliac disease in childhood and adolescence: latent and transient coeliac disease].

UNLABELLED: Coeliac disease (CD) is known as a lifelong condition of gluten intolerance. In case of some patients, the time after which gluten exposition leads to damage of the small intestinal mucosa may be very long. In addition to the florid form of CD, there are also silent (atypical mono- and oligosymptomatic with typical damage of the small intestinal mucosa) and latent forms (often asymptomatic without clear mucosal changes, antibody titres often normal). Occasionally the development of gluten tolerance is postulated (transient CD). We investigated 47 subjects diagnosed in childhood definitely as CD patients. In the age of 16.3 +/- 4.8 years, the patients started a gluten containing diet. After 6 to 9 months of gluten containing diet a small intestinal biopsy was performed in all patients. Surprisingly we found 11 patients with normal small intestinal mucosa (group 1). The other 36 patients showed a flattened mucosa as expected (group 2). The further development of group 1 was followed. In 9 patients a further biopsy was performed after more than 2 (at maximum after 8.1) years of gluten containing diet. In all patients the morphology of the mucosa was normal. In 7 of 11 cases normal numbers of intraepithelial lymphocytes were counted. Only in two patients raised titres of gliadin and endomysium antibodies were found after 4.5 and 15 years of gluten containing diet. In the other 9 patients no increase in antibody titers was found up to 10.3 years. However, in group 1, mucosal lactase activity was decreased as was also the case for group 2. CONCLUSION: A high number of adolescent coeliac patients does not respond or responds only minimally to reintroduction of gluten into the diet over a period longer than two years. These patients should regularly be further controlled serologically.

Adolescent↗

[Musculoskeletal biopsies in an open 0.5-T-MR system].

INTRODUCTION: MR-guided interventions have been successful in different medical disciplines. The aim of this paper is to report our results with the application of MR-guided biopsies of musculoskeletal lesions using an open 0.5-T-MR scanner and further to discuss these results on the basis of the available literature. PATIENTS AND METHODS: Between 1998 and 2003 30 patients (average age 44.1 years) underwent a total of 31 biopsies. The interventions were performed in an open 0.5-T MRI system using an active optical localization system as well as a navigation system. For the motion tracking we used T (1)-weighted real-time sequences with 0.25 pictures per second. For the sampling MR-compatible instruments were used that were specially developed for this purpose. The data of this retrospective investigation are based on the evaluation of the patient documents and the radiological findings. On the basis of the histological findings the technical success rate and the histological overall accuracy were determined. RESULTS: In 81 % of the biopsies the histological diagnosis was correct. In cases of suspected inflammation the histological accuracy was smaller (70 %). No differences were observed between skeletal and soft-tissue lesions. The technical success rate amounted to 77.5 %. No procedural or anesthesiological complications occurred. The mean operating time amounted to 65 min including the time for motion tracking. DISCUSSION: In cases of suspected lesions of the musculoskeletal system, the MR-guided biopsy represents a promising and safe procedure to get a histological diagnosis. In cases of sufficient size of the lesion sampling of a representative probe is possible. On account of the outstanding performance in soft-part contrasting, the sensitive structures surrounding the lesion can be saved. Substantial disadvantages of the procedure are the high costs for personal and material and the long operating time.

Adult↗

Protective effects of ambroxol in hypothermic liver preservation: a transplant study.

The bronchosecretolytic agent ambroxol added to histidine-tryptophan-ketoglutarate (HTK) solution has recently been shown to protect cold stored rat hepatocytes. The aim of the present study was to confirm these observations in a rat liver transplantation model. Before orthotopic liver transplantation, donor livers from 30 syngeneic Wistar rats were assigned to three groups (n = 10): (A) in situ flush (ISF) and 1/2-h cold storage (CS) with HTK solution, (B) ISF and 3-h CS with HTK, and (C) ISF and 3-h CS with HTK + 10(-3) mol/L ambroxol. The efficacy of the drug was evaluated by postoperative survival (> 14 days) and liver enzyme release (ALT), bile flow, histomorphological injury, and malondialdehyde (MDA) level in the grafts 15 min after reperfusion. After 1/2-h CS with HTK solution (A), 90% of the transplanted rats survived. In comparison with donor conditions, bile flow in the reperfused grafts decreased to 87 +/- 5.3%, whereas postoperative ALT levels slightly increased. After 3-h HTK preservation (B), the survival rate decreased to 60%, while ALT values markedly increased and bile flow after reperfusion declined to 82 +/- 6.6%. Ambroxol added to HTK solution (C) enhanced bile flow to 106 +/- 3.4%(p < .05), and reduced ALT and MDA levels and histomorphological injury of the transplanted livers, so that its beneficial effect in organ preservation has been confirmed in the transplant model. However, survival rate was not improved by the agent, probably because of the low cold ischemia tolerance of the Wistar rat livers used.

Alanine Transaminase↗

Hypoxia-induced tumour cell migration in an in vivo chicken model.

To investigate the relationship between hypoxia, neovascularisation and tumour cell spread, experiments on the area vasculosa of the early chick embryo under different oxygen concentrations were performed in vivo. Human glioblastoma cells (U-138MG) were inoculated onto the area vasculosa and the fertilised eggs were incubated under conditions of normoxia or hypoxia. For evaluation, we performed in vivo video-microscopy of the area vasculosa and determination of microvessel density (MVD), as well as a histological examination of the fixed specimen. Under hypoxia, MVD was significantly increased compared to normoxic conditions. Only under hypoxic conditions was tumour cell spread found outside the main tumour mass and within the vessels, at times followed by the subsequent development of secondary tumour cell bulks on the area vasculosa. These data lead to the conclusion that hypoxia can stimulate tumour cell migration in this in vivo model.

Animals↗

Differential expression and activity status of MMP-1, MMP-2 and MMP-9 in tumor and stromal cells of squamous cell carcinomas of the lung.

Matrix metalloproteinases (MMPs) play a key role in cancer progression. Interstitial collagenase (MMP-1) and type IV collagenases (MMP-2, MMP-9) are involved in the initial breakdown of collagen and basement membrane components during tumor growth and invasion. Besides tumor cells, fibroblasts are especially involved in MMP production. The aim of this study was to quantify MMP-1, MMP-2 and MMP-9 within tumor cells and tumor-surrounding fibroblasts compared to normal lung epithelial cells to gain an insight into the function of these MMPs in squamous cell carcinomas of the lung. The expression and activity of MMP-1, MMP-2 and MMP-9 were analyzed in 30 squamous cell carcinomas and in normal lung tissue from the same patients by immunohistology and gelatin zymography. The majority of tumor cells were positive for MMP-1 (mean +/- SD: 67.3 +/- 26.7%) and MMP-9 (64.7 +/- 22.8%), whereas a significantly lower percentage of normal bronchoepithelial cells (47.3 +/- 25.4 and 40.3 +/- 24.2%, respectively; p < 0.01) and fibroblasts located in the tumor-surrounding tissue (39.7 +/- 14.3 and 38.1 +/- 24.1%, respectively; p < 0.01) expressed these MMPs. Only a few tumor cells showed any immunoreactivity for MMP-2 (4.4 +/- 6.7%), whereas a higher percentage of fibroblasts tested positive for this enzyme (8.6 +/- 13.1%; p < 0.01). Using gelatin zymography, we could demonstrate that MMP-2 is activated in the tumor only, not in normal lung tissue. The coordinated expression of MMP-1, MMP-2 and MMP-9 in tumor cells and/or their induction in tumor-surrounding fibroblasts and further activation in the tumor tissue may be involved in the high invasive and metastatic potential of squamous cell carcinomas of the lung. Comparing the results from immunohistology and zymography can give indications for distribution and activity of proteinases, especially certain MMPs such as MMP-2.

Carcinoma, Squamous Cell↗

Influence of titanium coating on the biocompatibility of a heavyweight polypropylene mesh. An animal experimental model.

INTRODUCTION: In light of the fact that, to date, no information is available about titanium relative to its application in prosthetic material employed for hernial repair, the aim of the present work was to evaluate the fundamental possibilities of titanium-coated polypropylene meshes. MATERIALS AND METHODS: In experiments with animals, two groups, each containing 11 pigs, received either a heavyweight polypropylene mesh (Atrium) or an identical but titanium-coated mesh (titanium-coated Atrium) implanted into the left groin using the totally endoscopic extraperitoneal patchplasty technique. RESULTS: A significant difference in the shrinkage behavior between conventional Atrium and titanium-coated Atrium was found (14.9 vs. 8.8%, p < 0.05). Furthermore, the partial volume of the inflammatory infiltrate also proved to be smaller with the titanium-coated mesh (14.9 vs. 12.4%). In addition, Ki-67 expression was lower in the group implanted with titanium-coated mesh (21.0 vs. 15.0%). No difference was observed with regard to the apoptosis index (7.6 vs. 6.5). CONCLUSIONS: Heavyweight titanium-coated polypropylene meshes induce a less pronounced foreign body reaction in comparison with identical meshes with no titanium coating, which, since the amount of material implanted is identical, must be attributed solely to the titanium coating.

Animals↗