Screening for alimentary cancer: outstanding problems and a new strategy for research.
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Biomedical subjects
Publications and source records attributed to J Jankowski.
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This article is a review of aspects of the expression of the regulatory peptides; epidermal growth factor (EGF), transforming growth factor alpha (TGF-alpha), and their receptor (EGF-R) in the epithelium of the human oesophagus and stomach in health and disease. It has become clear that TGF-alpha has increased expression in metaplastic, dysplastic and neoplastic tissue of the oesophagus compared with normal mucosa. The degree of abnormal expression becomes more marked as dysplasia increases. TGF-alpha expression is also increased in gastric neoplasias. EGF has a different pattern of expression, being decreased in oesophagitis and increased in gastritis. Although EGF is present in Barrett's oesophagitis, the expression of EGF does not discriminate between dysplastic and neoplastic epithelium. EGF-R is normally expressed on all gastro-intestinal epithelia, but its expression is increased in Barrett's epithelium, as well as in adenocarcinomas of the oesophagus and the stomach. The two peptides bind to their receptors on the mucosal cell membranes, and the co-expression of peptide and receptor is positively associated with varying degrees of cellular proliferation. The density of receptor expression may modulate the proliferative stimulus, leading to either mitogenic (regulated) or oncogenic (unregulated) growth.
Hyperplastic polyps are common benign lesions of uncertain histogenesis, which occur in the colon in populations at risk for colorectal carcinoma. They contain neutral/MUC1 gene-related mucin which in turn is closely associated with the trefoil-peptide pS2, a major component of the ulcer-associated cell lineage, previously termed pseudopyloric metaplasia. We have examined 17 hyperplastic polyps for expression of the trefoil-peptides pS2 and human spasmolytic polypeptide by in situ hybridization and immunohistochemistry, as well as by using antisera to epidermal growth factor/urogastrone and its receptor and to epitopes of the product of the MUC1 gene to characterize any further similarity between these lesions and the ulcer-associated cell lineage and thus help elucidate the nature of the lesions. Our investigations show both human spasmolytic polypeptide and pS2 messenger RNA within the polyps, whereas only pS2 peptide could be demonstrated immunohistochemically. Epidermal growth factor/urogastrone, its receptor, and antisera to the MUC1 gene also showed widespread staining of these polyps. We suggest that hyperplastic polyps are formed of a lineage that both synthesizes and secretes trefoil-peptides and the MUC1 mucin and that hyperplastic polyps may be related to the phenotypically similar ulceration-associated cell lineage.
An x-ray apparatus like any other device becomes worn out. In order to avoid x-ray examinations of patients performed using a worn out apparatus a periodical control of such appliances should be carried out. This work presents a methodology based on simple quality tests for a standard x-ray apparatus. These tests measure parameters of x-ray tubes and beams of radiation. A positive feature of these tests is that they replace very expensive specialistic measuring equipment.
Selected parameters of coagulation and fibrinolysis were determined in 25 postmenopausal women, treated chronically for breast cancer with the use of tamoxifen. The significant influence of tamoxifen therapy on the serous fibrinolysis parameters was found. The time of euglobulin lysis was shorter, the concentration of alpha 2-antiplasmin decreased, and plasminogen concentration increased. The content of antithrombin III, fibrinogen, and caolin-cephalin time did not change significantly during therapy, except the prothrombin rate which increased. Tamoxifen is an important medicine with beneficial influence on the fibrinolytic system, without affecting the serous coagulation system.
The paper describes the organization and methods for assessment of occupational exposure of X-ray workers. The results of the dose measurements carried out during 1966-1991 at the Institute of Occupational Medicine in Lodz are discussed. In 1991 the measurements concerned about 25,500 persons employed in 2600 institutions. About 99.5% of the monitored population receives annual dose equivalent below 0.1 of the limit i.e. below 5 mSv. Doses exceeding the annual limit occur very rarely--a few cases a year.
Oesophageal cancer is a substantial cause of mortality in the Western world and recent data indicate that the incidence is increasing. Despite better understanding of the pathogenesis and in the surgical management of the disease, little improvement in the survival rates has been achieved anywhere in the world, especially because screening for detection of premalignant lesions cannot, at present, be adequately applied to populations at risk. The present review summarizes current knowledge of the use of conventional screening methods as well as possible applications of new techniques to targeted populations to permit earlier diagnosis of premalignant lesions of the oesophagus.
A 49-yr-old male was reviewed who had a 10-yr history of reflux esophagitis. He presented initially with frequent heartburn of moderate severity and, on subsequent endoscopy, was noted to have erosive esophagitis and, at that time, a high maximal gastric acid output. During the next 5 yr, his symptoms and acid output diminished. Eight years after presentation, he was noted to have developed a small area of Barrett's metaplasia, without dysplastic change. Ten years after the initial presentation he was completely asymptomatic, despite having extensive Barrett's metaplasia, now with high grade dysplasia. As a result, he was referred for esophagogastrectomy. At the time of surgery, he had alkaline reflux, with antacid gastric contents and, subsequently, hypochlorhydria was proven by a pentagastrin test. A second individual (male, 46 yr) who presented initially with reflux symptoms and gastric-type metaplasia, underwent gastric secretory studies that revealed a peak acid output of 16 mmol/L in 1986. During the period 1989 to 1991, his symptoms progressed despite H2 antagonist therapy. In this regard he was reinvestigated, and his peak acid output in 1991 was 0 mmol/L, and subsequent esophageal biopsies demonstrated intestinal metaplasia in four of six biopsies (two biopsies had high-grade dysplasia; the two others had gastric-type metaplasia). He has refused esophageal resection, and is being reviewed regularly at the endoscopy clinic. Flow cytometric analysis of the esophagus in both individuals revealed expression of epidermal growth factor receptor which was increased in the areas of high grade dysplasia, compared with Barrett's mucosa without dysplasia or normal cardiac mucosa. We conclude that alkaline reflux may accelerate the development of Barrett's esophagus (and intestinal type metaplasia) in patients with gastroesophageal reflux disease. The increased expressed of epidermal growth factor receptors in Barrett's mucosa with dysplasia compared with Barrett's mucosa without dysplasia may reflect the higher malignant potential of the former mucosa.
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Flow cytometry may be used to examine the properties of single or isolated cells. We have shown that it is possible to disaggregate and label oesophageal epithelial cells for two surface markers, CD15 and epidermal growth factor receptor. We have previously demonstrated these markers in oesophageal squamous cells using immunoperoxidase techniques. These labelled disaggregated cells could then be measured by flow cytometry.
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1. Epidermal growth factor and the related peptide transforming growth factor alpha have been implicated in the stimulation of gastric mucosal proliferation. We assessed the immunohistochemical distribution of these peptides and their receptor, epidermal growth factor receptor, in mucosa from the antrum and body of the stomach from 28 patients. Twenty-three of the 56 biopsies were histologically normal (12 antrum and 11 body), whereas the other 33 showed varying degrees of inflammation. 2. Epidermal growth factor, transforming growth factor alpha and epidermal growth factor receptor had maximal density of distribution on the apical surfaces of the superficial epithelial cells, but were also expressed to a lesser extent on neck and body cells of the glandular tissue (P less than 0.05). We also demonstrated that epidermal growth factor expression was greater in the epithelial cells of inflamed mucosa than in those of normal mucosa (P less than 0.05). 3. We assessed mucosal proliferation by the Ki-67 labelling index. Ki-67-positive cells were found predominantly in the neck area of the glands and were more frequent in glandular antral tissue than in body glandular tissue (P less than 0.05). Expression of epidermal growth factor receptor in the neck and isthmus cells had a significant correlation with the Ki-67 labelling index (P less than 0.05). 4. We conclude that epidermal growth factor and epidermal growth factor receptor may be important in the adaptation of gastric mucosa to inflammation.
1. The existence of specific glucose-6-phosphatase activity in human intestinal mucosa has been somewhat controversial. 2. We have demonstrated the presence of low levels of specific glucose-6-phosphatase activity in normal human adult intestinal mucosa. Activity was found in oesophagus, stomach, duodenum and colon. 3. Immunoblot analysis using antibodies monospecific for the 36.5 kDa liver glucose-6-phosphatase catalytic subunit demonstrated that intestinal mucosa contains low levels of the glucose-6-phosphatase enzyme protein. 4. The low levels of activity together with problems of proteolysis make human intestinal biopsies unsuitable for use in the diagnosis of type 1 glycogen-storage disease.
Epidermal growth factor (EGF) has been implicated in mitogenesis and oncogenesis in the gastrointestinal tract. To determine the role of EGF in oesophageal disease, its quantity and distribution in the oesophageal mucosa of control subjects and patients with oesophageal disease were studied. Oesophageal biopsy specimens, taken 20-40 cm from the incisors in 72 patients, were graded histologically and adjacent specimens were taken for immunohistochemical analysis of the distribution of EGF. In patients with Barrett's columnar lined oesophagus, specimens were also taken from the gastric cardia for comparison. Twenty two biopsy specimens showed oesophagitis, 20 Barrett's mucosa, and 30 were histologically normal. EGF was found in the capillary endothelium of the normal oesophageal papillae and basal mucosa. Significantly more EGF positive papillae were found in the normal mucosa (81%) than in the inflamed mucosa (42%) (p < 0.001). The 20 patients with Barrett's mucosa showed abnormal expression of EGF in 25% of the isthmus and superficial epithelial cells. This study has shown that EGF is found only in the endothelial cells of the capillaries of the normal oesophageal mucosa and that the peptide is detectable significantly less frequently than normal in the inflamed oesophageal mucosa. EGF is also abnormally present, in large quantities, in the cytoplasm of the epithelial cells of Barrett's mucosa compared with gastric mucosa.
The quantity and distribution of epidermal growth factor receptors (EGF-R) in oesophageal mucosa was studied in the oesophagus in order to determine its role in oesophageal disease. Fifty five biopsies were taken from different levels of the oesophagus in 25 consecutive patients undergoing endoscopy. Another group of eight patients with histologically proven Barrett's oesophagitis had a biopsy taken from the area of columnar lined oesophagus. A peripheral, membranous pattern was seen predominantly confined to the basal and immediately suprabasal cells in all of the first group of patients. In the superficial cells a few granular cytoplasmic structures were positive. All patients with Barrett's oesophagitis showed EGF-R staining of the surface epithelium. A computerised planimeter was used to determine the proportion of stained areas of squamous cells which were expressed as a percentage of the total area of squamous cells. The difference in the area of cells stained for EGF-R between normal and inflamed oesophageal mucosa (29.5% and 43.1% respectively) was significant (p less than 0.001).
This study was designed to correlate mucosal proliferation in Barrett's oesophagus with expression of a growth promoting peptide, transforming growth factor alpha (TGF alpha). Oesophageal mucosa was studied from 50 patients with oesophageal disease who had been treated by oesophagectomy. Histological analysis showed a range of oesophageal pathology - 18 patients had gastric type Barrett's mucosa, 18 had intestinal type Barrett's mucosa, and 14 had oesophageal adenocarcinomas. Sections were stained immunohistochemically for proliferating cell nuclear antigen (PCNA) (an index of cellular proliferation) and TGF alpha. PCNA immunostaining was seen mainly in the basal cells of the neck/foveolar epithelial compartment of the glands in Barrett's oesophagus. However, in mucosa with high grade dysplasia, the proliferative compartment extended upwards into the superficial layers of the glands. At least 2000 cells were counted in each patient to determine the proportion with PCNA immunoreactivity (PCNA labelling index). The labelling index was highest in adenocarcinoma (25%) and in Barrett's intestinal type mucosa with high grade dysplasia (26%) compared with intestinal type mucosa with no significant dysplasia (20%) and Barrett's gastric type mucosa (12%). There was a significant positive correlation between PCNA labelling indices and TGF alpha expression in Barrett's mucosa (p less than 0.01). In glands showing high grade dysplasia, TGF alpha immunoreactivity was seen in the same regions of the glands as PCNA immunoreactivity, indicating the possibility of involvement of TGF alpha in (pre) neoplastic proliferation in Barrett's oesophagus.
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