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Biomedical subjects

S Eggstein

Publications and source records attributed to S Eggstein.

12 recordsLinked to original sources
PubMed1996

Autocrine growth stimulation of SW403 colon carcinoma cell line is caused by transforming-growth-factor-alpha-mediated epidermal growth factor receptor activation.

Results of recent studies indicate that some cultured human carcinoma cell lines are capable of proliferating autonomously in serum-free medium as a result of the synthesis and secretion of transforming growth factor alpha (TGF alpha). TGF alpha interacts with epidermal growth factor receptor (EGFR) and induces its activation. In an attempt to extend these observations, we evaluated TGF alpha-mediated autonomous growth and constitutive EGFR activation in the human adenocarcinoma cell line SW403. The cell line shows synthesis of EGF receptors and TGF alpha but not EGF, and exhibits constitutive phosphorylation of the 170-kDa EGFR. Use of blocking anti-EGFR monoclonal antibodies (mAb) inhibits autonomous growth of SW403 cells and leads to a significant reduction of receptor phosphorylation. The inhibitory effect of the blocking anti-EGFR mAb is reversible upon addition of TGF alpha. In contrast, autonomous proliferation of SW403 cells is not inhibited by addition of neutralizing anti-EGF mAb. Our findings suggest that the proliferation of cells of the human SW403 adenocarcinoma cell line is regulated by an autocrine TGF alpha loop and that this regulatory pathway can be interrupted by using anti-EGFR mAb.

Adenocarcinoma↗
PubMed1996

Raf-1 kinase, epidermal growth factor receptors, and mutant Ras proteins in colonic carcinomas.

Epidermal growth factor receptors (EGFR) and ras mutations are known to play a significant role in controlling cell growth and tumor promotion. Both of them transmit mitogenic signals to the nucleus by activation of Raf-1 kinase. In this study, the expression of EGFR and mutant Ras proteins, and, for the first time, the expression, phosphorylation and kinase activity of Raf-1 kinase have been determined in paired samples of colorectal cancer and mucosa. The tumor and mucosa samples did not differ significantly with regard to Raf-1 kinase content and activity. A major difference between tumors and mucosa was found, however, in the phosphorylation of Raf-1. Most of the mucosa samples (13/20), but only 1/20 of the cancer samples, contained hyperphosphorylated Raf-1. EGFR were significantly (p = 0.0025) decreased in the tumors. The decreased phosphorylation of Raf-1 in colonic carcinomas could be the result of activation of Raf-1 phosphatases or inactivation of kinases phosphorylating Raf-1. New forms of treatment based on EGFR overexpression do not seem to be suitable for the majority of colonic cancers.

Adenocarcinoma↗
PubMed1995

Expression of GM-CSF and a functional GM-CSF receptor in the human colon carcinoma cell line SW403.

Only little is known about the expression of a functional granulocyte-macrophage colony-stimulating factor receptor (GMR) and its ligands in human colon carcinoma cell lines. To obtain more information on this subject, we investigated the human colon carcinoma cell line SW403, and we were able to demonstrate the constitutive synthesis of a 85-kDa GMR in SW403 cells. After stimulation with 10% fetal calf serum, GM-CSF transcripts were expressed as well. The incubation of SW403 cells with GM-CSF resulted in an intensive down-regulation of the activity of the interferon-gamma-receptor gene, which could be reconstituted by simultaneous addition of an anti-GM-CSF antibody. GM-CSF induced an activation of tyrosine-phosphorylated protein kinases with molecular weights in the range of 30 to 210 kDa, but it had no effect on the DNA synthesis of SW403 cells.

Adenocarcinoma↗
PubMed1995

Expression of gastrin, gastrin/CCK-B and gastrin/CCK-C receptors in human colorectal carcinomas.

To investigate further the presence of an autocrine proliferative loop involving gastrin in colorectal carcinomas and to clarify the receptor responsible, 102 human colorectal carcinomas and 10 hepatic metastases were investigated for the expression of the genes encoding gastrin, the gastrin/CCK-B receptor and the gastrin/CCK-C receptor. Levels of RNA expression were assayed by RNase protection assay. In addition, gastrin/CCK receptors on crude membranes of tumour tissue were assayed by radioligand binding. High-affinity gastrin/CCK-B receptors were not detected in any of the carcinomas investigated, whereas in 36% low-affinity binding was observed, consistent with the expression of the gastrin/CCK-C receptor. RNase protection assay detected the RNA for the gastrin/CCK-B receptor in 11% of the carcinomas investigated, whereas the RNA for the gastrin/CCK-C receptor was demonstrated in 75% and the RNA for gastrin in 86% of the carcinomas investigated. These results confirm the recent demonstration of progastrin fragments in colorectal carcinomas. One possible explanation for progastrin expression is that such progastrin fragments may participate in an autocrine proliferative loop. The receptor involved in this loop is more likely to be the low-affinity gastrin/CCK-C receptor rather than the gastrin/CCK-B receptor, which is rarely expressed in colorectal carcinomas.

Binding, Competitive↗
PubMed1995

[Therapy and follow-up of gastroesophageal chemical burns].

We report a retrospective analysis of 61 patients admitted during the years 1974 to 1992 after having recently swallowed a corrosive agent. Within 24 hours, the localisation, severity and extent of the injury had been determined by endoscopy. In 13 patients the injury was restricted to the oropharynx, and in 48 it involved esophagus, stomach and duodenum. Fourteen had sustained a second degree injury, and 16 a third degree injury. Out of five patients with third degree injuries who were treated by operation within the first three days, two survived. Two patients operated upon for complications after 10 days of conservative treatment died. The total mortality was 21%, but 56% for those who had received a third degree injury. Thirteen patients developed a stenosis (27% of those with gastroesophageal lesions). Esophageal strictures were dilatated with bougies, but stomach stenoses were treated by resection. Of the 12 patients treated by dilatation, 4 sustained perforations and 4 of them were free of symptoms for a considerable period of time (more than 4 years).

Adolescent↗
PubMed1994

Radiation enteropathy.

PURPOSE: Radiation enteropathy presents a complex clinical picture which varies from case to case. Diagnosis and treatment require a thorough knowledge of the natural history of the condition and of the complications which are to be expected. PATIENTS AND METHODS: The pathogenesis, clinical picture, diagnosis and treatment of radiation damage to the gut are described. The progress of 90 patients operated on in the Chirurgische Universitätsklinik Freiburg is retrospectively evaluated. RESULTS: Haemorrhage, vomiting, diarrhoea and, occasionally, perforation are the signs of acute radiation enteropathy, which appears weeks or months after radiotherapy. Except for perforations, these can usually be treated conservatively. Chronic radiation enteropathy does not manifest itself until years after irradiation, with diarrhoea, obstruction and the development of fistulae. The acute ileus can often be relieved with decompression tubes. After localising the stenosis radiologically with a contrast medium, and improvement in the general condition, many cases require operative intervention. This usually consists of resection, the establishment of a bypass anastomosis or enterostomy. In 44% of the patients postoperative complications followed, with a mortality of 22%. The cause of the high complication rate is partly the poor general condition of the patient, and partly the radiation induced impairment in wound healing, which may lead to insufficiency of the anastomosis and the development of fistulae. CONCLUSIONS: The treatment of radiation enteropathy is a demanding task. Because of the high complication rate, it is generally wise to choose the least risky procedure.

Adult↗
PubMed1994

[The value of CEA immunoscintigraphy for diagnosis of colorectal cancer and its metastases: results of a prospective study].

The importance of the CEA-immunoscintigraphy (IS; BW 431/26 Fa Behring) for the diagnosis of colorectal carcinoma and its metastases was determined in a prospective trial including 60 patients. The results were compared with results of the ultrasound, the CT-Scan and the Angio-CT. Patients suffered from a colorectal carcinoma (15), from a local tumor recurrence after bowel resection (10), from hepatic (39) and/or extrahepatic metastases (16). In 40 patients the diagnosis was confirmed by laparotomy. Regarding the detection of hepatic metastases the sensitivity and specificity of the Angio-CT were superior to the IS (0.86 and 0.63 vs. 0.78 and 0.45). Ultrasound and Angio-CT together revealed true positive results in 89.2%. The IS did not improve this rate. Regarding the detection of extrahepatic metastases the sensitivity and the specificity of the CT were slightly superior to the IS (0.59 and 0.87 vs. 0.47 and 0.28). However, the IS increased the rate of true positive results by 18.8% (US + CT 43.7%; +IS 62.5% true positive results). Due to these results the IS is not recommended as the method of choice to detect liver metastases. But in patients unfit for diagnostic laparotomy the IS may give additional information of the extrahepatic tumor stage.

Adult↗
PubMed1992

[Serum gastrin level in patients with colorectal adenoma or carcinoma].

During the last years interest has focused on the trophic effect of gastrin in colorectal carcinomas. Some reports indicated an increased serum level of gastrin in patients with colorectal adenomas or carcinomas. In a prospective study in 261 patients submitted to colonoscopy fasting serum gastrin concentrations were determined. 91 patients served as control, 89 patients had one or more adenomas, 55 patients suffered from a colorectal carcinoma, 17 had a benign, postoperative stenosis of the colon, and 9 had a chronic inflammatory bowel disease. All patients fulfilled the following criteria: No regular drug intake, no previous gastric or small bowel operation, no known ulcer disease, no abnormalities in serum calcium, creatinine, triglycerides, cholesterol and blood urea. Mean gastrin level was 86.63 +/- 23.8 pg/ml in the control, 84.57 +/- 25.1 pg/ml in the adenoma group and 84.6 +/- 24.4 pg/ml in the carcinoma group. No difference of serum gastrin levels were observed regarding sex, age, tumor stage and localisation.

Adolescent↗
PubMed1991

Influence of gastrin, gastrin receptor blockers, epidermal growth factor, and difluoromethylornithine on the growth and the activity of ornithine decarboxylase of colonic carcinoma cells.

Polyamines are essential factors of cell growth and differentiation. Modulation of the cellular polyamine content by 2-difluoromethylornithine (DFMO) inhibiting ornithine decarboxylase (ODC), or by hormones inducing ODC, influences cell growth. Gastrin acts trophically on some colonic carcinomas and their growth is inhibited by gastrin receptor blockers. The mechanism of the trophic action of gastrin on colonic carcinomas is not known. In this study the effect of gastrin, gastrin receptor blockers, epidermal growth factor (EGF) and DFMO on growth and ODC activity of four human colon carcinoma cell lines (SW 403, SW 1116, LS 174 T and Lovo) was investigated. Growth and ODC activity of all cell lines were inhibited by DFMO. Growth of the SW 403 cell line was increased by gastrin and inhibited by the gastrin receptor blocker benzotrypte. The other cell lines did not respond to gastrin and the gastrin receptor blocker. In SW 403 cells ODC activity was increased by gastrin, and was also elevated after treatment with the gastrin receptor blocker. These in vitro results were confirmed by studies on tumours that developed from SW 403 cells in nude mice. Combination of benzotrypte and DFMO did not enhance the antiproliferative effect. EGF increased growth of SW 403 cells, but no induction of ODC activity was measured. LS 174 T cells were not stimulated by EGF. Medium replacement was the strongest stimulus of ODC activity in SW 403 cells already inducing ODC after 3 h. During cell culture ODC activity was high after seeding and decreased continuously with increasing cell density. These data suggest that gastrin induces ODC in gastrin-sensitive colonic carcinoma cells. DFMO appears to be a valuable antiproliferative agent in colonic carcinoma cells.

Animals↗
PubMed1989

Growth of colorectal carcinoma cells: regulation in vitro by gastrin, pentagastrin and the gastrin-receptor antagonist proglumide.

The growth-regulating effects of pentagastrin, gastrin and the gastrin-receptor antagonist proglumide were investigated in three established cell lines derived from human colorectal carcinomas in vitro and after transplantation into nude mice. In vitro a significant increase of cell growth in the SW 403 cell line incubated with pentagastrin or gastrin was observed. In the Lovo cell line this effect was only detected after synchronization of cell growth. Pentagastrin and gastrin had no effect on the growth of the Ls 174 T cell line. Proglumide reduced cell proliferation in all three cell lines as well as in the L929S cell line derived from fibroblasts, which served as control. After transplantation into nude mice all tumor cell lines increased, Lovo and Ls 174 T as undifferentiated tumor, SW 403 as differentiated. Pentagastrin increased and proglumide decreased growth in SW 403 tumors, whereas no effect was observed on Ls 174 T and Lovo tumors. We therefore conclude that growth of some colorectal carcinomas is regulated by gastrin, but that the effect of proglumide is unspecific rather than related to blockage of gastrin receptors. The growth-regulating effect of gastrin could be due to tumor differentiation.

Animals↗
PubMed1989

[Dipeptidyl aminopeptidase IV in hospitalized patients and in galactosamine hepatitis of the rat: Activity and lectin affinity chromatography in serum and hepatic plasma membranes].

The activity of dipeptidyl aminopeptidase IV was studied in the sera of 378 hospitalized patients. The mean activity of dipeptidyl aminopeptidase IV was elevated significantly in patients with neoplasmata and hepatitis, but not in patients with liver cirrhosis. Significant correlations (p less than 0.001) existed with gamma-glutamyl transferase, glutamate dehydrogenase, alkaline phosphatase and leucine aminopeptidase. A significant correlation with lactate dehydrogenase existed only in patients with neoplasmata. Principal component analysis, performed with aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, leucine aminopeptidase, lactate dehydrogenase and dipeptidyl aminopeptidase IV, revealed correlations between the activities of aspartate aminotransferase and alanine aminotransferase, and between alkaline phosphatase and leucine aminopeptidase, but neither dipeptidyl aminopeptidase IV nor lactate dehydrogenase showed any correlation with either of these two groups. In lectin affinity chromatography with concanavalin A and wheat germ lectin sepharose, serum dipeptidyl aminopeptidase IV from liver cirrhosis patients showed the same binding pattern as that from healthy subjects. The activity and glycosylation of dipeptidyl aminopeptidase IV in serum and hepatic plasma membranes was investigated in rats, following the induction of hepatitis with galactosamine. In the serum, dipeptidyl aminopeptidase IV activity was elevated as early as 6 h after galactosamine injection, and the elevated activity persisted until the 7th day. At the same time dipeptidyl aminopeptidase IV activity was also elevated in the hepatic plasma membrane. Ninety eight percent of hepatic dipeptidyl aminopeptidase IV bound to concanavalin A as well as to wheat germ lectin and this value was unchanged during hepatitis. In the serum of control rats, 90% of dipeptidyl aminopeptidase IV bound to concanavalin A but only 39% to wheat germ lectin.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗