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Biomedical subjects

A Tannapfel

Publications and source records attributed to A Tannapfel.

At least 19 recordsLinked to original sources
PubMed1998

Apoptosis, proliferation, bax, bcl-2 and p53 status prior to and after preoperative radiochemotherapy for locally advanced rectal cancer.

PURPOSE: To investigate the relationship between apoptotic cell death, proliferative activity, and the expression of apoptosis regulating proteins in rectal cancer prior to and after radiochemotherapy. MATERIALS AND METHODS: In 32 patients dispositioned to receive preoperative radiochemotherapy for locally advanced rectal carcinoma, pretherapy biopsies and the final resected specimen after radiochemotherapy were available for analyses. Apoptotic cells were identified and quantified using in situ end labeling (ISEL) technique. The expression of the bax protein was assessed immunohistochemically. Additionally, double immunostaining was performed for apoptotic cells and bax expression. The proliferative activity was determined by immunohistochemical assessment of the Ki67 (MIB-1) and the proliferating cell nuclear antigen (PCNA). p53- and bcl-2 expression was analyzed immunohistochemically. A clinical-to-pathologic downstaging after radiochemotherapy was achieved in 25 of 32 patients (78%). During follow-up, tumor recurrence was observed in six cases. In one case, no residual tumor was detected after radiochemotherapy. RESULTS: After radiochemotherapy, the apoptotic index increased significantly in almost every case examined. In contrast, the proliferative activity was significantly decreased in resected specimens as compared to biopsies. Bax immunostaining was detected in 12/31 (39%) biopsies and in 26/31 (84%) resected specimens. In the resected specimen, significantly more apoptotic cells that were bax-positive were found than in biopsies. Bcl-2 immunostaining occurred in 15/31 biopsies and 12/31 resected specimens, respectively. Tumors that were immunohistochemically negative for p53 (20/31 [65%]) generally exhibited a higher apoptotic index and a high expression level of bax than p53-positive tumors (11/31 [35%]). However, we did not find any correlation between the (pre- and post-therapeutic) rate of apoptosis or the level of bax expression and the degree of clinical-to-pathologic downstaging or the frequency of tumor recurrence. CONCLUSION: Our results indicate that radiochemotherapy is associated with an increase in bax expression and also in apoptotic cell death. The observation of higher rates of apoptosis and bax in p53-negative tumors suggests that p53 might be a possible regulating factor of apoptosis in rectal cancer.

Adult↗
PubMed1998

[Proliferation and apoptosis before and after preoperative simultaneous radiochemotherapy of rectal carcinomas].

PURPOSE: To investigate the relationship between apoptotic cell death, proliferative activity, and the status of the tumor suppressor gene p53 in rectal cancer before and after radiochemotherapy. MATERIALS AND METHODS: Thirty-two patients dispositioned to receive preoperative radiochemotherapy for locally advanced rectal carcinoma prior to radical surgical tumor resection were analysed. In all cases, pretherapy biopsies and the final resected specimens after radiochemotherapy were available for analyses. Apoptotic cells were identified and quantified using in situ end labeling (ISEL) technique. The proliferative activity was determined by immunohistochemical assessment of the Ki67 (MIB-1) antigen. p53 expression was analysed immunohistochemically as well. A clinical-to-pathologic downstaging after radiochemotherapy was achieved in 25/32 patients (78%). In one case, no residual tumor was detected after radiochemotherapy. RESULTS: After radiochemotherapy, the apoptotic index increased significantly in almost every case examined. In contrast, the proliferative activity was significantly decreased when comparing biopsies and resected specimens. Tumors that were immunohistochemically negative for p53 generally exhibited a higher apoptotic index than p53 positive tumors. However, we did not find any correlation between the (pre- and post-therapeutic) rate of apoptosis and the degree of clinical-to-pathologic downstaging. CONCLUSION: Our results indicate, that radiochemotherapy induces an increase in apoptotic cell death. The observation of higher rates of apoptosis in p53 negative tumors suggests that p53 might be a regular of apoptosis in rectal cancer.

Adenocarcinoma↗
PubMed1998

Distribution and pharmacokinetics of Photofrin in human bile duct cancer.

Prognosis of patients with bile duct tumors is mostly poor due to late diagnosis and a lack of adequate curative and palliative treatment modalities. To evaluate the potential of photodynamic therapy (PDT) as a novel and alternative treatment approach, we have investigated the uptake and tumor-specific localization of the photosensitizer Photofrin in human biliary tract neoplasms. We have quantified the distribution and the pharmacokinetics of Photofrin in normal and tumor tissue biopsies of the human bile duct by quantitative fluorescence microscopy and digital image analysis of cryosections. Fluorescence intensities (expressed as a percentage of a standard) are 19.0 +/- 11.4% and 25.2 +/- 12.7% for tumors and 10.9 +/- 2.9% and 13.2 +/- 9.1% (mean +/- SD) for normal bile duct tissue at 24 h (n = 5) and 48 h (n = 8) after Photofrin administration (2 mg kg-1 i.v.), respectively, and decrease afterwards in normal bile duct tissue over the period of investigation (4-35 days). The ratios of fluorescence in tumor versus normal tissue are found to be 1.7 +/- 0.7 and 2.3 +/- 1.2 (mean +/- SD) at days one and two after Photofrin administration, respectively. Thus, Photofrin preferentially accumulates in bile duct neoplasms, reaching peak values during the first two days. These data suggest that laser irradiation should be performed within this period after Photofrin injection to achieve tumor selectivity of PDT for effective treatment of bile duct carcinoma.

Adenocarcinoma↗
PubMed1998

Primary amyloidosis of the mesentery and the retroperitoneum presenting with lymphedema.

We report the case of a 57-yr-old woman presenting with moderate weight loss, abdominal distension, and lymphedema of the legs and vulva. Computed tomography of the abdomen revealed massive thickening of the rectal wall, mesentery, and retroperitoneum. Primary amyloidosis was diagnosed by immunohistochemistry from the rectum and duodenum. To our knowledge, lymphedema due to primary amyloidosis has not yet been reported. The diagnosis should be presumed in the case of retroperitoneal thickening and lymphedema and can be established by immunohistochemistry.

Amyloidosis↗
PubMed1997

[Cronkhite-Canada syndrome. Epidemiology, symptoms, morphology and therapy based on a case report and literature review].

Juvenile polyposis was first described by Cronkhite and Canada in 1955. This disease is characterized by juvenile intestinal polyps and ectodermal abnormalities. The etiology of Cronkhite-Canada syndrome (CCS), however, is still not well understood. Interestingly among patients with CCS a significant correlation (16.5%) with intestinal carcinomas has been observed. Thus, malignant transformation and/or genetic predisposition may be involved in the initiation of the disease. In the following, epidemiology, symptoms, morphology and therapy of CCS are discussed. Our examinations are based on studies reported in the literature and on a case report of a female patient who developed a colon carcinoma 2 years after initial diagnosis of CCS.

Adenocarcinoma↗
PubMed1997

Multiple simultaneous gastric carcinomas.

A total of 1664 patients with gastric cancer were examined to evaluate the rate of multiple synchronous primary tumours. In cases of multiple synchronous cancer (MSC), the tumours were analysed immunohistochemically for their expression pattern of p53, c-erbB2, ras, E-cadherin and proliferative activity. Multiple synchronous gastric carcinomas (MSCs) were observed in 61 out of 1664 patients (3.7%), with a total of 134 carcinomas. In our series, early carcinoma was observed more frequently in MSC than in solitary cancers. The comparison of tumour stage in MSC and solitary tumours revealed that multiple early gastric cancers were significantly more often of type I (protruded type) and IIa (superficial elevated type) than solitary early cancer. Multiple advanced carcinomas were more often of a lower pT category than solitary advanced gastric cancer. Performing immunohistochemistry for p53, c-erbB2 and ras in 134 tumours with MSCs, we observed positivity rates of 33%, 59% and 87% respectively. In 43 patients, the multiple tumours in each individual patient demonstrated an identical status of p53 and c-erbB2, and in 42 patients a similar pattern of E-cadherin expression was observed. The proliferative index, determined by proliferating cell nuclear antigen (PCNA) immunolabelling, did not differ significantly between the MSC in each patient. Ras immunostaining was detected in 53 out of 61 patients, but also in metaplasia and regenerative hyperplasia in the specimens. In survival analysis, no difference was observed between patients with solitary or multiple early or advanced carcinomas. Our results suggest that in at least a high proportion of patients with gastric cancer multiple primary tumours arise from precancerous conditions leading to similar genetic alterations.

Aged↗
PubMed1997

Systemic infection with Mycobacterium genavense following immunosuppressive therapy in a patient who was seronegative for human immunodeficiency virus.

We describe, to our knowledge, the first case of disseminated Mycobacterium genavense infection in a patient who was seronegative for human immunodeficiency virus. The patient, a 47-year-old woman, had been previously treated with immunosuppressive drugs for 9 months to control an unclassified immunologic disorder characterized by intermittent fever and inflammatory pulmonary, hepatic, and dermal infiltrates. Antemortem and postmortem examinations revealed the presence of numerous mycobacteria in the bone marrow, spleen, kidneys, and lungs; these organisms failed to grow in vitro and were identified as M. genavense by 16S rRNA gene sequencing. This case illustrates that systemic M. genavense infections are not restricted to patients with AIDS but can also occur in otherwise immunocompromised patients.

Female↗
PubMed1997

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↗
PubMed1996

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↗
PubMed1996

[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↗
PubMed1996

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↗
PubMed1995

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↗
PubMed1994

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↗