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R Porschen

Publications and source records attributed to R Porschen.

At least 73 records · Page 4Linked to original sources
PubMed1994

p53 protein expression and prognosis in squamous cell carcinoma of the esophagus.

BACKGROUND: The p53 gene product is known to regulate cell growth and proliferation. Whereas the wild-type p53 protein suppresses cell growth, the mutated p53 protein acts as an oncogene. Mutations in the p53 gene usually result in p53 protein stabilization and accumulation; so that the gene product can be detected by immunohistochemistry. Recently, the immunohistochemical detection of the p53 protein was associated with prognosis in breast, colorectal, and other types of cancer. However, its prognostic role in esophageal cancer remains to be elucidated. METHODS: p53 expression in formalin fixed, paraffin embedded samples of 204 patients with primary squamous cell carcinoma of the esophagus, who underwent esophageal resection, were analyzed immunohistochemically with DO-1, a monoclonal antibody that detects wild-type and mutant forms of p53. The relationship between p53 immunoreactivity and prognostic factors was determined by the Chi-square test, and the prognostic impact of p53 protein expression was analyzed using univariate and multivariate survival analyses. RESULTS: In 137 of 204 tumors (67.2%), nuclear immunoreactivity for the p53 protein was detected. There was no correlation with sex, age, pathologic tumor (pT) category, pathologic lymph node (pN) category, metastasis (M) category, residual cancer (R) category, histologic grade, or preoperative radiation therapy. In contrast to clinicopathologic parameters, p53 expression was not correlated with prognosis in univariate and multivariate survival analyses. CONCLUSIONS: The p53 protein can be detected by immunohistochemistry in a high percentage of squamous cell carcinomas of the esophagus. However, the overexpression of the p53 gene product has no impact on the prognosis.

Adult↗
PubMed1994

Vascularization of carcinomas of the esophagus and its correlation with tumor proliferation.

Vascularization and tumor cell proliferation were analyzed in 33 resected human squamous cell carcinomas of the esophagus using the endothelium-specific antibody BW 200 and the proliferation-associated antibody Ki-67. Vascular parameters (relative capillary volume, relative total vessel volume, vascular surface area, and vascular length) as well as the percentage of proliferating tumor cells (Ki-67 index) were evaluated on frozen sections by a morphometric method. Vascular parameters of the normal mucosa exceeded those of tumors significantly, by a factor of 1.4-2.3. The mean distance between tumor capillaries and the onset of necrosis was 92 +/- 34 microns. Global vascular density did not correlate with TNM stage, tumor diameter, or overall tumor proliferation (mean Ki-67 index, 35.1%; range, 14.2-64.1%). However, a significant negative correlation existed between the percentage of proliferating tumor cells per tumor cord and the intercapillary distance between capillaries located at the edges of these cords. This observation points to the fact that the esophageal cancers were composed of multiple tumor cords and that each of these cords possessed its own supply capillaries at the base of the cord. The sum of these "supply units" thus constitutes an esophageal cancer. The intercapillary distance may reflect the oxygenation status of tumor cells, which cannot be predicted on the basis of tumor staging or grading.

Aged↗
PubMed1994

Growth inhibition of human gastrointestinal cancer cells by cyclosporin A.

We have studied the ability of cyclosporin A (CsA) to inhibit the growth of human AGS gastric and HT29 colon carcinoma cells in vitro. Using continuous drug exposure in growth assays of cultured tumour cells we found that CsA produced a dose-dependent growth inhibition in gastric and colon cancer cells with a half-maximal effect at 5 microM and 6 microM CsA respectively. The growth inhibition of CsA was reversible in AGS cells, when the tumour cells were incubated in normal growth medium following CsA treatment. Trypan blue dye exclusion in AGS cells indicated a cytostatic rather than a cytotoxic effect in the concentration range used. Coincubation of CsA-treated cells with 10-400 U/ml interleukin-2 (IL-2) could not abrogate this growth inhibition, suggesting an IL-2 independent mechanism of action. Flow-cytometric analysis did not reveal a phase arrest of the gastric cancer cells within the cell cycle. We conclude from our experiments that CsA cytostatically and reversibly inhibits the growth of human gastric cancer cells in a dose-dependent manner. In contrast to its mechanism of action in lymphocytes, this direct antiproliferative effect of CsA seems not to be mediated by an IL-2-dependent pathway or a cell-cycle-phase arrest of the tumour cells.

Adenocarcinoma↗
PubMed1994

[Chemotherapy and radiochemotherapy of colorectal cancers: adjuvant and palliative therapeutic procedures].

Palliative treatment in metastatic colorectal carcinoma is primarily based on 5-fluorouracil. The remission rates have been improved by biomodulation and by continuous infusion of 5-FU. Adjuvant treatment for carcinoma of the colon and rectum is used in subgroups of patients in order to improve the results of surgical treatment. After curative resection of a colonic carcinoma with lymph node metastasis (TNM stage III) treatment with levamisole and 5-FU is indicated. As the risk of local failure is increased in carcinoma of the rectum adjuvant pelvic radiation therapy is used, eventually combined with systemic chemotherapy. In order to define the subgroups of patients who might profit by palliative or adjuvant treatment and in order to develop more effective combination therapies patients should be entered into prospective randomized trials.

Antineoplastic Agents↗
PubMed1993

Prognostic significance of DNA ploidy in adenocarcinoma of the pancreas. A flow cytometric study of paraffin-embedded specimens.

BACKGROUND: The prognostic significance of tumor DNA ploidy in patients with cancer of the pancreas has not been defined because conflicting results have been reported. METHODS: DNA content was measured in 56 ductal adenocarcinomas of the pancreas. DNA ploidy status was evaluated by flow cytometry in nuclei isolated from paraffin-embedded tumor tissues. RESULTS: An abnormal DNA stemline was observed in 27 (48%) patients. The percentage of aneuploid tumors was significantly increased in tumors classified as Stage III/IV (53%) compared with those classified as Stage I (22%). A borderline significant association existed between DNA ploidy and radicality of surgery (P = 0.08). The median survival of patients with diploid carcinomas was 6.9 months (standard error, +/- 0.9) in comparison to 4.5 +/- 1.2 months for patients with aneuploid tumors (P = 0.013 by generalized Wilcoxon test; P = 0.023 by generalized Savage test). Although a selection bias cannot be excluded, survival of patients with a radical resection was longer than that of patients with a nonradical resection (P = 0.0008 and P = 0.0085, respectively). In addition, presence of distant metastasis (P = 0.0006 [Wilcoxon test] and P = 0.033 [Savage test]) could be identified as a prognostic factor. In a Cox regression model, results of surgery and DNA ploidy were independent prognostic variables. CONCLUSIONS: Because DNA ploidy has a significant impact on prognosis in pancreatic cancer, it should be used as a variable for stratified randomization of patients in therapeutic trials.

Adenocarcinoma↗
PubMed1993

In situ evaluation of the relationship between epidermal-growth-factor-receptor status and tumor-cell proliferation in colon carcinomas.

The association between the expression of the epidermal-growth-factor receptor (EGFR) and tumor proliferation was studied in 69 resected human adenocarcinomas of the colon. EGFR was detected immunohistochemically using the monoclonal antibody (MAb) EGFRI. Tumor-cell proliferation was assessed with the MAb Ki-67 directed against a proliferation-associated nuclear antigen expressed only in proliferating cells. The percentage of Ki-67-positive tumor cells (Ki-67 index) was evaluated by the point-counting method. Forty-seven carcinomas contained detectable EGFR immunoreactivity. Statistical analysis failed to reveal correlations between the EGFR status and T, N and M stages or tumor differentiation. The mean Ki-67 index did not differ between EGFR-positive and -negative carcinomas. Seven tumors contained clearly distinguishable areas with different EGFR staining intensity. In these tumors with a locally heterogeneous EGFR expression, tumor proliferation also did not correlate with EGFR immunoreactivity. These in situ observations suggest that EGFR expression may not play an important role in the growth regulation of human colonic carcinomas.

Adenocarcinoma↗
PubMed1993

Protein kinase C and adenylate cyclase as targets for growth inhibition of human gastric cancer cells.

In the human gastric adenocarcinoma cell line AGS the effects of the protein-kinase-C-activating phorbol ester 12-O-tetradecanoylphorbol 13-acetate (TPA), the protein kinase C inhibitor staurosporine, the adenylate-cyclase activating agent forskolin, and the permeable dibutyryl-adenosine 3',5'-monophosphate (Bt2cAMP) on the proliferation were assessed. Cell counting followed 5 days of incubation. Prolonged activation of protein kinase C by TPA, inhibition of protein kinase C by staurosporine, activation of adenylate cyclase by forskolin or a direct increase of the intracellular cAMP level all result in a dose-dependent growth inhibition of AGS gastric tumour cells. Half-maximal inhibition was achieved at 100 pM for TPA, 1 nM for staurosporine, 20 microM for forskolin, and 600 microM for Bt2cAMP. It is concluded that protein kinase C and adenylate cyclase play a fundamental role in the growth of AGS gastric cancer cells. Interference with these enzymes involved in the signal transduction of growth regulation in tumour cells may represent a target in the development of new antiproliferative principles.

Adenocarcinoma↗
PubMed1993

Influence of preoperative radiotherapy on DNA ploidy in squamous cell carcinomas of the oesophagus.

The influence of preoperative radiotherapy on the prevalence of DNA aneuploidy and the prognostic significance of tumour DNA ploidy was evaluated in 126 patients with squamous cell carcinoma of the oesophagus. Preoperative radiotherapy with 30 Gy was performed in 52 patients. DNA ploidy was analysed by flow cytometry on nuclei isolated from paraffin embedded tumour tissue. DNA aneuploidy was identified in 75 tumours (61%) and found to correlate significantly with tumour stage. The percentage of aneuploid carcinomas was significantly reduced by preoperative radiotherapy (surgery only group, 71%; radiotherapy group, 47%, p = 0.01). Although the median survival time was slightly better in the diploid than in the aneuploid group (11.3 and 8.0 months respectively), this difference was not statistically significant. A curative tumour resection was the most important prognostic factor. Preoperative radiotherapy did not prolong survival in oesophageal cancer.

Aged↗
PubMed1993

[Perioperative multi-modality treatment strategies in esophageal cancer].

In order to improve the prognosis of patients with cancer of the esophagus, perioperative combined treatment modalities have been designed. The positive effect of an additional preoperative chemotherapy and of a pre- or postoperative radiotherapy has not been proven consistently until now. Neoadjuvant radiochemotherapy induces a pathohistologic complete remission in one quarter of the patients. The results of radiochemotherapy without operation in esophageal carcinomas look promising. However, their exact value has still to be investigated in randomized studies.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1993

Fecal occult blood testing: comparative evaluation of a two-hole versus a three-hole single slide test.

The aim of this study was to analyze the effectiveness of the three-hole fecal occult blood test hemoCARE in the detection of colorectal neoplasia in asymptomatic individuals in comparison with the conventional two-hole single slide test Hemoccult. Tests were distributed to 10,269 subjects older than 45 years. A total of 62.8% of the participants returned both tests, which were positive in 374 (5.8%). The diagnostic evaluation of 208 cases revealed 57 colorectal adenomas and carcinomas. The hemoCARE test was associated with a larger number of false-positive results than the Hemoccult test (p < 0.01). Fecal occult blood testing with the three-hole test demonstrated a significant increase in the yield of colorectal neoplasms as compared with the two-hole test (57 vs. 48 detected colorectal neoplasms; p < 0.01) without modifying the positive predictive value.

Colorectal Neoplasms↗
PubMed1992

DNA aneuploidy in Crohn's disease and ulcerative colitis: results of a comparative flow cytometric study.

DNA ploidy and S-phase fractions were assessed by flow cytometry in colonic biopsy specimens from 28 patients with ulcerative colitis and 51 with Crohn's disease. Whereas only diploid DNA histograms were found in Crohn's disease and control subjects, three patients with ulcerative colitis exhibited DNA aneuploidy. In one case, aneuploidy was associated with low grade dysplasia. S-phase fractions were higher in ulcerative colitis (mean (SD) 17.8 (7.7)%) than in Crohn's disease (13.1 (4.6)%) or control subjects (14.2 (4.6)%), but did not correlate with either disease activity or duration in any group. In this study, aneuploidy was associated exclusively with ulcerative colitis, even in the absence of dysplasia. In view of the epidemiological differences in malignant colonic transformation between ulcerative colitis and Crohn's disease, this study suggests that flow cytometry may help to identify individuals with an increased cancer risk in ulcerative colitis.

Aneuploidy↗
PubMed1992

[Risk of colorectal cancer in ulcerative colitis--monitoring strategies and identification of risk patients].

Patients with ulcerative colitis carry an increased colorectal cancer risk. The cumulative cancer risk for patients with pancolitis is 0.5-0.7% per patient year. Dysplasia as a histologic marker of a neoplastic transformation is used to identify patients with an increased cancer risk during colonoscopic surveillance. Because the classification of dysplasia is subject to inter- and intraobserver variation new methods for the detection of risk patients have been investigated. DNA analysis by flow cytometry seems to be of value for the detection of DNA aneuploidy and the identification of patients who are at risk for neoplastic progression. The significance of DNA aneuploidy is being evaluated in prospective studies. Surveillance guidelines depend on duration and anatomical extent of the colitis as well as on the detection of dysplasia.

Cell Transformation, Neoplastic↗
PubMed1992

[DNA ploidy and dysplasia in ulcerative colitis--interim analysis of a prospective study].

DNA ploidy and cell cycle phases were evaluated by flow cytometry in colonic biopsy specimens from 107 patients with ulcerative colitis in order to analyse the prevalence of DNA aneuploidy as an indicator of numerical chromosomal aberrations and the cell proliferation in all forms of ulcerative colitis. Whereas G2/M-phase fractions in ulcerative colitis and in controls were comparable (2.7 +/- 1.1% vs. 2.8 +/- 1.1%), S-phase fractions in ulcerative colitis exceeded those of controls (7.5 +/- 3.2% vs. 6.5 +/- 2.3%; p < 0.01). In 28 control patients, only diploid DNA histograms existed. Single or multiple aneuploid stem lines were detected in 10 patients with ulcerative colitis (9.3%). Aneuploidy was nearly exclusively associated with pancolitis. Dysplasia was present in 13 patients (indefinite: 8; low-grade: 5), of whom 5 patients also showed DNA aneuploidy. 5 patients with non-dysplastic mucosa exhibited DNA aneuploidy. Because dysplasia and DNA aneuploidy can be discordant and might therefore identify different subgroups at risk, flow cytometry might play a role as a valuable complement to histological examination in surveillance programs of ulcerative colitis.

Adult↗