ISSN:0253-4886    

DOI:10.1159/000172239

出版商:S. Karger AG    

年代:1994

数据来源: Karger

ISSN:0253-4886    

DOI:10.1159/000172240

出版商:S. Karger AG    

年代:1994

数据来源: Karger

ISSN:0253-4886    

DOI:10.1159/000172241

出版商:S. Karger AG    

年代:1994

数据来源: Karger

摘要:

Mucosal ulceration in the gastrointestinal tract leads to the development of a novel cell lineage which locally secretes growth factors such as trefoil peptides and epidermal growth factor (EGF). Gastric mucosal ulceration causes an increase of EGF receptor density and a profound decrease of somatostatin receptor density in the mucosal ulcer margin and scar. These changes in growth factors and their receptors cause a strong increase of cell proliferation in the ulcer margin. In experimental ulcer models, EGF and basic fibroblast growth factor (bFGF) promote ulcer healing by increasing epithelial cell proliferation and angiogenesis, respectively. Indomethacin delays ulcer healing by decreasing epithelial cell proliferation, inhibition of angiogenesis, and inhibition of remodelling of the granulation tissue in the ulcer base. Indomethacin interferes with EGF binding and proliferative response of gastric cultured KATO III cells. In addition, bFGF cannot reverse indomethacin-induced deleterious effects on experimental gastric ulcer healing. In summary, growth factors play an important role in promoting wound healing in benign gastrointestinal diseases.

ISSN:0253-4886    

DOI:10.1159/000172242

出版商:S. Karger AG    

年代:1994

数据来源: Karger

摘要:

The molecular alterations that contribute to the histomorphological changes in chronic pancreatitis are completely unknown. The purpose of our studies in the past several years was to investigate the importance of growth factors and growth factor receptors in chronic pancreatitis. Using immunohistochemistry, Northern blot analysis and in situ hybridization we found a marked overexpression of the epidermal growth factor (EGF) receptor and c-erbB-3. In addition, the pancreas of patients with chronic pancreatitis and pancreatic head enlargement overexpressed c-erbB-2. Polypeptide growth factors such as EGF and transforming growth factor alpha that bind to the EGF receptor were also overexpressed in many chronic pancreatitis samples. Furthermore, enhanced mRNA levels encoding acidic fibroblast growth factor and basic fibroblast growth factor were detectable. These findings indicate a role for growth factors and growth factor receptors in the pathophysiology of chronic pancreatitis and suggest that these factors might contribute to the morphological alterations that occur in chronic pancreatitis in humans.

ISSN:0253-4886    

DOI:10.1159/000172243

出版商:S. Karger AG    

年代:1994

数据来源: Karger

摘要:

This paper draws attention to the similarities between the response of the major pancreatic ducts and the luminal gastrointestinal tract to injury. In chronic inflammation of both of these tissues, cells appear which appear to have the capability of secreting epidermal growth factor/urogastrone, and it is proposed that this peptide has the ability to induce the expression of a series of further peptides, the trefoil peptides pS2 and hSP. These peptides have been shown to have motogenic effects on epithelial cells, and it is proposed that the further study of their expression in pancreatic diseases, and of their action of the pancreatic epithelium, will prove productive.

ISSN:0253-4886    

DOI:10.1159/000172244

出版商:S. Karger AG    

年代:1994

数据来源: Karger

ISSN:0253-4886    

DOI:10.1159/000172245

出版商:S. Karger AG    

年代:1994

数据来源: Karger

摘要:

Historically, the role for transforming growth factor-βs (TGF-βs) in malignancy has been difficult to prove. TGF-βs are potent autocrine and paracrine negative regulators of the growth of normal epithelial and neuroectodermal cells in vitro. Therefore we hypothesized that the aberrant growth of tumor cells and neoplastic development, in general, may be due to a loss of growth regulation by TGF-β. By immunohistochemistry, using isoform specific antibodies raised to synthetic peptides of each TGF-β isoform, and by in situ hybridization, using non-cross-hybridizing cRNA probes to each TGF-β isoform, we examined the protein and mRNA expression of TGF-β, respectively, in a variety of carcinomas and gliomas compared to normal tissue. The analysis of the cell types that synthesized the messge for TGF-β isoforms compared to those which synthesized the protein indicated whether TGF-β functioned by an autocrine or paracrine mechanism of action in thes

ISSN:0253-4886    

DOI:10.1159/000172246

出版商:S. Karger AG    

年代:1994

数据来源: Karger

摘要:

Tumor necrosis factor-α (TNF-α), a macrophage-synthesized cytokine, not only modifies the expression of one of its own receptors on pancreatic tumor cells, it also regulates the expression of the platelet-derived growth factor, of the transforming growth factors alpha (TGF-α) and TGF-β and of the epidermal growth factor receptor (EGF-R). Stimulation of mRNA and protein expression of EGF-R and of its ligand TGF-α is effected by TNF-α binding to TNF receptors with a molecular weight of 55 kd (TNF-RI) and 75 kd (TNF-RΠ). The registered increase of TNF-RII involves the second messenger protein kinase C and phospholipases as well. Simultaneously TNF-RII induces a decrease of the ERBB2 receptor expression which heightened TNF-α sensitivity regarding its cytotoxicity. Concerning TNF-RII a selective signal pathway in TGF-α induction was proved with the help of specific antibodies. Furthermore the upregulation of the EGF-R antigen density in pancreatic tumor cell lines offers a point of attack for antibody-mediated cytotoxicity. A partially complete remission of xenografts of the pancreatic tumor cell lines in vivo includes a cellular defense mediated by the Fc area of the antibody and opens up new perspectives in clinical

ISSN:0253-4886    

DOI:10.1159/000172247

出版商:S. Karger AG    

年代:1994

数据来源: Karger

摘要:

Ras is thought to play a major role in the pathogenesis of pancreatic cancer. It normally functions by relaying mitogenic signals initiated by cell surface receptors into the cytoplasm and nucleus. In pancreatic cancer a high incidence of Ras activation by point mutations was found. Activated Ras initiates a cascade of protein kinase activation. These serine/threonine kinases in turn lead to activation of transcription factors localized in the nucleus, which bind to enhancer elements in genes involved in mitogenesis. Experimentally this has been shown by utilizing loss of function mutants of transcription factors which can inhibit Ras-induced transformation. Furthermore there is evidence that these transcription factors can be phosphorylated by these kinases in in vitro assays. These signal transduction pathways should be analyzed in pancreatic cancer and might elucidate new targets for therapy.

ISSN:0253-4886    

DOI:10.1159/000172248

出版商:S. Karger AG    

年代:1994

数据来源: Karger