Biomedical subjects

A Tannapfel

Publications and source records attributed to A Tannapfel.

129 records · Page 8Linked to original sources

PubMedDate not supplied

Microvessel density and endothelial cell proliferation after amifostine (Ethyol) administration in vivo.

BACKGROUND: As amifostine is rapidly metabolised by the membrane-bound and capillary alkaline phosphatase to the active metabolite WR-1065, microvessel density in normal and cancer tissue may influence the therapeutic potential of the pro-drug WR-2721. Thus, it is of interest how the administration of amifostine itself alters vascular density. MATERIALS AND METHOD: For this study fertilized eggs were used and 0.05 ml amifostine (25.7 micrograms) was injected into the area vasculosa. As controls untreated area vasculosa were examined as well as eggs treated with 0.05 ml NaCl 0.9%, 48 hr after injection the vascular density was determined by histometrical methods. Applying the LAB method we performed immunohistochemical analysis of the proliferating cell nuclear antigen of endothelial cells. RESULTS: There was a significant (p < 0.001) difference in vascular density with a mean microvessel count of 25.08 (+/- 8.45 SD) vascular intersections/mm2 in the untreated control, 30.40 (+/- 12.84 SD) in the NaCl control and 53.69 (+/- 24.56 SD) in the amifostine treated area. There was also a significant (p < 0.001) difference in endothelial cell proliferation (PCNA) between untreated controls with a mean PCNA positivity of 14.05 (+/- 5.28 SD) and amifostine treated area vasculosa with a mean PCNA positivity of 32.22 (+/- 18.14 SD). CONCLUSION: A single dose administration of 25.7 micrograms amifostine induces endothelial cell proliferation and subsequent neovascularisation in the area vasculosa of the fertilised egg.

Amifostine↗

PubMedDate not supplied

Apoptosis and cell proliferation in the metaplasia-dysplasia-carcinoma-sequence of Barrett's esophagus.

BACKGROUND/AIMS: The regulation of apoptosis as a distinctive form of cell death and proliferation in the process of carcinogenesis in Barrett's esophagus is poorly understood. To investigate regulation of apoptosis, proliferation and the participation of the tumor suppressor gene p53, we examined these parameters in Barrett's metaplasia, dysplasia, and adenocarcinoma. METHODOLOGY: Apoptotic cells were identified and quantified in tissue specimens of 45 patients with different stages of Barrett's esophagus and normal fundus epithelium, respectively, using the in situ end-labeling and electron microscopy method in combination with morphological criteria. The tumor suppressor gene p53 was examined by direct sequencing of exon 4-8 as well as immunohistochemically. The proliferative activity was assessed by Ki67 immunostaining. RESULTS: Apoptotic cell death, identified by the in situ end-labeling and ultrastructural technique was significantly increased in Barrett's epithelium with intestinal metaplasia than in specimens with normal fundic epithelium and Barrett's carcinomas (P < 0.01). The proliferative activity, defined as Ki67 labeling index, was highest in adenocarcinomas (P < 0.01). P53 mutations were found in 8/9 adenocarcinomas and 2/5 specimens with dysplasia. Apoptosis was lower in p53 positive specimens of the metaplasia-dysplasia-carcinoma-sequence than in p53 negative specimens of Barrett's esophagus (P < 0.05). CONCLUSIONS: The higher levels of both apoptosis and proliferation indicate an increased cell turnover in Barrett's epithelium. Apoptosis seems to maintain tissue homeostasis, which is regulated by p53, and gradually lost in the metaplasia-dysplasia-carcinoma-sequence of Barrett's esophagus.

Adenocarcinoma↗

PubMedDate not supplied

Incidence of apoptosis, cell proliferation and P53 expression in renal cell carcinomas.

BACKGROUND: Given the growing evidence that proliferation indices may be of prognostic significance in renal cell carcinoma and that parameters of cell loss (usually, but not exclusively due to programmed cell death) are biologically relevant, identification and quantitation of apoptosis and possible regulatory factors are of considerable clinical importance. MATERIALS AND METHODS: Apoptotic cells were identified and quantified in a series of 87 curatively-resected (R0) renal cell carcinomas using the in situ end labeling method in combination with morphological criteria. The proliferative activity was determined by immunohistochemical assessment of the MIB-1 (Ki-67)-and proliferating cell nuclear antigen (PCNA). The immunoreactivity of p53 was analysed using the DO7 antibody. Immunostaining of p53 has been linked to the accumulation of mutant p53 protein. The results obtained were compared with UICC pathohistological stage and grade and finally with disease-related survival rate. RESULTS: In each carcinoma examined, we could demonstrate apoptosis of varying degrees with in a range from 1 to 19 and with a median of 5. Immunostaining of p53 suggested the presence of mutant p53 in 24/87 (28%). A reciprocal correlation was found between apoptosis and p53-positivity in terms of significantly less apoptosis in p53-positive tumors. Positive statistical correlations were seen between the tumor grade and MIB-1/PCNA positivity and apoptosis. In univariate survival analysis, stage and grade, MIB-1 and PCNA index and apoptotic index were significantly related to prognosis. Multivariate Cox disease-related survival analysis revealed that stage of disease and MIB-1 were significant independent prognostic factors. CONCLUSIONS: These results indicate that apoptosis and cell proliferation are strongly related in renal cell carcinoma and that the presence of mutant p53 seems to be a negative regulator of apoptosis. In univariant survival analysis, apoptosis was, in addition to other parameters, of prognostic significance. However, multivariate analysis found that only the stage of the disease and MIB-1 were independent prognostic factors.

Apoptosis↗