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Identification of antileucoprotease in remodelled human adult nasal surface epithelium.

Antileucoprotease (ALP) is generally considered as a specific marker for glandular serous cells, and plays a major role in the defence of the respiratory tract against proteolytic damage. Nevertheless, several studies have identified ALP in bronchial and bronchiolar surface epithelial cells, and also an increased number of ALP-containing cells in bronchiolar tissue during the development of pulmonary diseases. In order to define more clearly whether the surface epithelium might be involved in the defence of the respiratory mucosa, we have investigated the expression of ALP by cells of the nasal surface epithelium. Indirect immunocytochemistry and in situ hybridization for ALP were performed on human nasal polyp sections. The height of the surface epithelium, its morphology, and the degree of local inflammation were assessed in parallel. Surface epithelium morphology was highly heterogeneous. ALP-containing cells were identified, but only in remodelled areas of the surface epithelium (foldings, basal cell and/or mucous cell hyperplasia), with no association to the degree of inflammation. These results demonstrate that the surface epithelial cells of the human adult nasal mucosa can express ALP in remodelled surface epithelium, and may be actively involved in the biochemical defence of the airways.

Epithelium↗

Pseudomonas aeruginosa adherence to remodelling respiratory epithelium.

Pseudomonas aeruginosa is an opportunistic organism, which frequently colonizes the respiratory tract of patients with impaired host defence. In cystic fibrosis (CF) patients, this pathogen causes a progressive destructive bronchitis and bronchiolitis and is responsible for high mortality. Normal respiratory epithelium is protected against bacteria via mucus and mucociliary clearance. Alteration of mucociliary clearance and of glycosylation of mucins in CF facilitates the access of bacteria to the underlying airway epithelial cells. Intact respiratory epithelium does not bind P. aeruginosa, whereas injured respiratory epithelium is highly susceptible to P. aeruginosa adherence. We found that the high affinity of respiratory epithelium, from CF and non-CF sources, for P. aeruginosa, during the wound repair process is related to the apical expression of asialo ganglioside M1 (aGM1). The affinity of repairing respiratory epithelium for P. aeruginosa is time-dependent, and is related to transient apical expression of aGM1 at the surface of repairing respiratory epithelial cells. CF respiratory epithelial cells apically express more aGM1 residues with relation to an increased affinity for P. aeruginosa than non CF cells. High epithelial damage followed by repair represents a major cause of P. aeruginosa adherence to airway epithelium in cystic fibrosis. However, P. aerurignosa adherence and colonization are not restricted to cystic fibrosis disease and P. aeruginosa pneumonia may also occur in severely immunocompromised patients, suggesting that epithelial injury and decreased host-response favour the colonization of the airways by P. aeruginosa.

Bacterial Adhesion↗

Apoptosis in uterine epithelium and decidua in response to implantation: evidence for two different pathways.

During the initial steps of implantation, the mouse uterine epithelium of the implantation chamber undergoes apoptosis in response to the interacting blastocyst. With progressing implantation, regression of the decidual cells allows a restricted and coordinated invasion of trophoblast cells into the maternal compartment. In order to investigate pathways of apoptosis in mouse uterine epithelium and decidua during early pregnancy (day 4.5-7.0 post coitum), we have investigated different proteins such as TNFalpha, TNF receptor1, Fas ligand, Fas receptor1, Bax and Bcl2 as well as caspase-9 and caspase-3 using immunohistochemistry. To detect cells undergoing apoptosis the Tunel assay was performed. Immunoreactivity for TNFalpha as well as for TNF receptor1 was observed exclusively in the epithelium of the implantation chamber and the adjacent luminal epithelium from day 4.5 post coitum onwards. In the developing decidua the Fas ligand, but not the Fas receptor, was expressed. Bax and Bcl2 revealed a complementary expression pattern with Bax in the primary and Bcl2 in the adjacent decidual zone. Strong immunolabelling for the initiator caspase-9 was restricted to the decidual compartment, whereas caspase-3 expression characterized the apoptotic uterine epithelium. Only some caspase-3 positive decidual cells were found around the embryo which correlated to the pattern of Tunel staining. Taken together, the apoptotic degeneration of the uterine epithelium seems to be mediated by TNF receptor1 followed by caspase-3, whereas the very moderate regression of the decidua did not show the investigated death receptor, but Bax and Blc2 instead and in addition caspase-9, which indicates a different regulation for epithelial versus decidual apoptosis.

Animals↗

Arginine vasopressin and atrial natriuretic peptide do not alter ion transport by cultured fetal distal lung epithelium.

Previous studies have shown that i.v. arginine vasopressin (AVP) decreases but does not stop lung fluid secretion in term fetuses not in labor. Although it has been presumed that the response to AVP results from augmented sodium transport, there is controversy whether AVP actually does affect sodium transport in mammalian lung epithelium. To determine if AVP or aldosterone could alone or together augment sodium transport in the perinatal lung, we studied primary cultures of fetal rat distal lung epithelium in Ussing chambers. The short circuit current of these sodium-transporting cells was not affected by the application of either 30 or 300 mU/mL AVP whether or not they were previously exposed to aldosterone (10(-6) M). Aldosterone also did not affect the baseline bioelectric properties. Short circuit current increased in response to 8-bromo cAMP (10(-4) M) and 3-isobutyl-1-methylxanthine (10(-3) M) to levels 169 +/- 16 (SEM) and 172 +/- 7% of respective baseline values. AVP had no effect in cells pretreated with 3-isobutyl-1-methylxanthine. Monolayers also did not respond to atrial natriuretic peptide (10(-11) to 10(-8) M). Monolayers of Na-absorbing A6 renal epithelium did increase short circuit current with either aldosterone or AVP. AVP increased endogenous cAMP levels in A6 but not fetal rat distal lung epithelium cells, suggesting that fetal rat distal lung epithelium lacks V2 receptors. These studies demonstrate that AVP does not increase ion transport in cultured fetal distal lung epithelium although these cells possess the necessary second messenger system.

Aldosterone↗

Branching morphogenesis of embryonic mouse lung epithelium in mesenchyme-free culture.

Embryonic mouse lung epithelium was separated from its mesenchyme and cultured under mesenchyme-free conditions. When covered with Matrigel, the cultured epithelium underwent branching morphogenesis in medium containing acidic fibroblast growth factor (aFGF), in which the epithelial cells constructed a simple columnar cell layer forming a lumen, as seen in normal development. The epithelial growth and branching morphogenesis induced by aFGF was completely inhibited by an antibody against aFGF. Heparin caused extra epithelial growth in cooperation with aFGF, but its use resulted in luminal expansion instead of enhanced branching. Basic FGF induced abnormal morphogenesis of the epithelium, though the lumen formed was lined by a simple columnar cell layer. Epidermal growth factor could not maintain epithelial cell growth, and the epithelium became a smaller and smoother ball than that at the start of cultivation. When covered with a collagen gel instead of Matrigel, the epithelium remained in its initial form, neither newly branching nor becoming a smooth ball, in the presence of aFGF. These results show that the epithelium of lung rudiments was able to branch under mesenchyme-free culture conditions in which a basement membrane matrix and aFGF were substitutes for the mesenchyme.

Animals↗

Fibroblast growth factors are necessary for neural retina but not pigmented epithelium differentiation in chick embryos.

During eye development, optic vesicles evaginate laterally from the neural tube and develop into two bilayered eye cups that are composed of an outer pigment epithelium layer and an inner neural retina layer. Despite their similar embryonic origin, the pigment epithelium and neural retina differentiate into two very distinct tissues. Previous studies have demonstrated that the developmental potential of the pigmented epithelial cells is not completely restricted; until embryonic day 4.5 in chick embryos, the cells are able to switch their phenotype and differentiate into neural retina when treated with fibroblast growth factors (FGF) (Park, C. M., and Hollenberg, M. J. (1989). Dev. Biol. 134, 201-205; Pittack, C., Jones, M., and Reh, T. A. 1991). Development 113, 577-588; Guillemot, F. and Cepko, C. L. (1992). Development 114, 743-754). These studies motivated us to test whether FGF is necessary for neural retina differentiation during the initial stages of eye cup development. Optic vesicles from embryonic day 1.5 chick were cultured for 24 hours as explants in the presence of FGF or neutralizing antibodies to FGF2. The cultured optic vesicles formed eye cups that contained a lens vesicle, neural retina and pigmented epithelium, based on morphology and expression of neural and pigmented epithelium-specific antigens. Addition of FGF to the optic vesicles caused the presumptive pigmented epithelium to undergo neuronal differentiation and, as a consequence, a double retina was formed. By contrast, neutralizing antibodies to FGF2 blocked neural differentiation in the presumptive neural retina, without affecting pigmented epithelial cell differentiation. These data, along with evidence for expression of several FGF family members and their receptors in the developing eye, indicate that members of the FGF family may be required for establishing the distinction between the neural retina and pigmented epithelium in the optic vesicle.

Animals↗

Laryngeal granuloma: characteristics of the covering epithelium.

The purpose of the present study was to evaluate the biological behaviour of the marginal epithelium, that proliferates and eventually covers laryngeal granulomas, and to reveal the applicability of the recently re-introduced Ljubljana classification when reporting reactive epithelial hyperplastic lesions. A retrospective clinical and histomorphological analysis was performed on 149 laryngeal granuloma biopsies. Epithelial changes were classified according to the Ljubljana classification into normal epithelium; simple, abnormal, or atypical hyperplasia; and carcinoma in situ. Atrophic epithelium, not evaluated separately in the Ljubljana classification, was additionally assessed. Simple hyperplasia was found in 98 cases (65.8 per cent), abnormal hyperplasia in seven (4.7 per cent), atrophic epithelium in 24 (16.1 per cent), and normal squamous epithelium in 20 (13.4 per cent). Atypical hyperplasia and carcinoma in situ were not observed. The results of our study clearly showed that the proliferation of the covering epithelium mostly in the form of simple hyperplasia, is entirely reactive and therefore reversible. No epithelial hyperplastic lesions were found that were previously described to be associated with an increased risk of malignant alteration, namely atypical hyperplasia and carcinoma in situ. However, since an initial growth of an invasive malignant neoplasm might macroscopically imitate the appearance of laryngeal granuloma, a histological examination in all aetiological forms of laryngeal granulomas is required. By clearly discerning the benign nature of epithelial changes in laryngeal granulomas, the recently re-evaluated and further formulated Ljubljana classification may also influence the clinical handling of patients.

Adolescent↗

Does occurrence of keratinizing stratified squamous epithelium in the middle-ear cavity always indicate a cholesteatoma?

The origin and behaviour of keratinizing stratified squamous epithelium, an essential component of cholesteatoma occurring in the middle-ear cavity, has puzzled otologists for decades. In this experimental study in 16 cats, central (n = 23) and peripheral (n = 9) tympanic membrane perforations were observed for up to 63 days before sacrifice. The tympanic membranes with bony rim were excised, decalcified and embedded in Epon 812. Sections were stained with toluidine blue and examined using a light microscope. The perforation had been sealed by meatal epithelium exhibiting pronounced hyperplasia and keratin formation, lying on a bed of granulation tissue. Subtotal central perforations healed within 14 days, forming a bowl-shaped tympanic membrane and leaving parts of the handle of the malleus (with meatal epithelium) protruding freely into the middle-ear cavity. Stratified squamous epithelium, morphologically identical with that of external ear canal epidermis, could be observed on the malleus even 63 days after operation. This meatal epithelium was non-keratinizing, non-invasive, and showed no destructive properties typical of acquired cholesteatoma. During certain circumstances, the cell cycle of hyperplastic epidermal epithelium within the middle-ear cavity can evidently be arrested and inactivated by a local defence mechanism.

Animals↗

Fine structure of the dorsal epithelium of the tongue of the Japanese terrapin, Clemmys japonica (Cheloia, Emydinae).

As reptiles are situated phylogenetically between the amphibians and the mammals, they exhibit considerable variation in the structure of their tongues. The present study, one of a series of studies on reptile tongues, aims to demonstrate the three-dimensional structure of the dorsal lingual surface of a turtle, the Japanese terrapin Clemmys japonica, and to clarify the ultrastructural features of the lingual epithelial cells. In the study lingual papillae were observed by scanning electron microscopy to be widely distributed over the dorsal surface of the tongue. Irregularly shaped (conical, columnar or angular) papillae were located in the anterior and central areas, and ridge-like ones, in the latero-posterior area. Histological examination revealed that the connective tissue penetrated into the core of the papillae, and the epithelium was of a stratified squamous and/or cuboidal type. Under the transmission electron microscope, two types of cells were identified in the intermediate layer of the apical epithelium of the lingual papilla: one type was probably an immature mucous cell, whereas the other was elongated in a baso-apical direction, its cytoplasm containing fine granules. In the surface layer of the apical epithelium, typical mucous cells and cells containing numerous, fine, electron-lucent granules were recognized. Both types of cells possessed microvilli on their free-surfaces. In the lateral epithelium of the lingual papillae, the cytological features from the basal layer to the superficial intermediate layer were essentially the same as in the apical epithelium. However, in the surface layer, mucous cells were significantly larger in number than in the apical epithelium.

Animals↗

Proliferative activity of cyst epithelium in human renal cystic diseases.

Increased proliferative activity of the renal tubular epithelium is thought to be a prerequisite for renal cyst formation by many investigators. However, in humans, the exact in vivo proliferation rate of epithelial cells lining these cysts is not known. In this study, which used immunohistochemical methods with an antibody to proliferating cell nuclear antigen (PCNA), the proliferation index (PI) (percentage of PCNA positive cell nuclei among epithelial cells lining the renal cysts) was determined in 10 cases of autosomal dominant polycystic kidney disease (ADPKD), 8 cases of autosomal recessive polycystic kidney disease (ARPKD), and 8 cases of acquired cystic kidney disease (ACKD). Cysts with proximal and distal nephron phenotype and cysts with markedly thickened basement membranes, as well as cysts lined by atrophic (flattened), "regular" (cuboidal or cylindrical), and hyperplastic epithelium, were evaluated separately. The overall PI of cyst epithelium (excluding hyperplastic cysts) was 2.58 in ADPKD, was 10.5 in ARPKD, and was 3.61 in ACKD. Overall, there were only minor differences in the PI between the various types of cysts. Cysts with hyperplastic epithelium in ACKD (unlike in ADPKD) showed a high PI (9.1). For comparison, the PI of two renal cell carcinomas occurring in two ACKD cases was also determined (13.70 and 8.67%). The PI of tubular epithelium in normal kidneys was only 0.22 to 0.33%, depending on the tubule segment. In contrast, in polycystic kidneys, those noncystic segments of the nephron from which the cysts are thought to originate (distal nephron (specifically collecting duct)) in ARPKD, primarily distal in ADPKD, proximal and distal in ACKD, had PI values similar to those of the cyst epithelium.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗

Elimination of epithelium from healing postsurgical periodontal wounds by ultra-low temperature. Initial observations.

Prevention of epithelial migration into healing postsurgical periodontal wounds may enhance connective tissue attachment. This study attempted to destroy selectively epithelium on gingival flap surfaces by ultra-low temperature. Sixteen sites in four young adult cats received subcrestal reverse bevel incisions followed by sulcular incisions. Full thickness periodontal flaps were reflected, the remaining supracrestal soft tissue surrounding the teeth was removed, and exposed root surfaces were curetted. Narrow zones measuring about 4 mm along the coronal margins of the flaps were exposed to ultra-low temperature for 5 seconds using a gas expansion cryoprobe cooled to -81 degrees C and placed at the oral gingival aspects of the flaps. Flaps were then repositioned and sutured. Control sites were sham-operated with the cryoprobe kept at room temperature (25 degrees C). Gingival biopsies were taken at 1 hour and at 2, 4, 8 and 12 days following surgery. Microscopically, 1-hour postfreezing and control specimens appeared similar. At 2 and 4 days, large surface areas of corium were denuded of epithelium or were covered by necrotic debris. Mild inflammatory responses were noted within the corium. At 8 days, the epithelium almost completely covered the corium with some initial formation of crevicular epithelium. After 12 days, crevicular epithelium was observed in all tissue sections. No significant morphologic damage to the connective tissue was noted at any time. We, therefore, concluded that low cryodoses can effectively destroy oral gingival epithelium without causing significant morphologic damage to the underlying lamina propria at this level of observation.

Animals↗

Characterization of the peri-implant epithelium in hamster palatine mucosa: behavior of Merkel cells and nerve endings.

The purpose of this study was to investigate the relationship between Merkel cells and nerve elements during tissue regeneration after receiving dental implants. Golden hamsters were divided into 3 groups and titanium alloy implants were fixed in their left-side maxilla through the third palatine rug. Animals were sacrificed at 1, 2, 3, 4, 5, 6, and 7 days after the implantation and tissues were characterized at the immunohistochemical and morphological levels. CK 20 and PGP 9.5 antibodies which react with Merkel cells and nerve fibers were used. Immunohistochemically, no CK 20-positive Merkel cells were seen in the peri-implant epithelium throughout the 7 days. However, starting at day 4, PGP 9.5-positive nerve fibers appeared in the connective tissue, and by day 7, nerve fibers had invaded the more superficial layer of the peri-implant epithelium compared to the mucosa removal control group. At the electron microscopic level, the intercellular spaces of the regenerating epithelium in the mucosa removal control group were small. In contrast, intercellular spaces of the peri-implant epithelium tended to be wide and regenerating nerve fibers invaded those intercellular spaces. In both the mucosa removal control group and the implantation group, the basal lamina and connective tissues regenerated completely. However, clear Merkel cells containing neurosecretory granules were not observed. Taken together, our results indicate that Merkel cells in the hamster palatine mucosa do not regenerate in the peri-implant epithelium. However, regenerative nerve fibers seem to play essential roles as part of the defense and sensory systems around the peri-implant epithelium to compensate for the weakened defense mechanism.

Animals↗

The intermediate epithelium lining the larynx of the Suncus murinus.

In the larynx of the Suncus murinus the stratified squamous epithelium lines the tip of the caudal surface of the epiglottis and the region close to the vocal process of the arytenoid cartilage, while the ciliated columnar epithelium is located in the laryngeal sac and the dorsal part of the vocal fold. Further, in the transitional zone between the stratified squamous epithelium and the ciliated columnar one there exists the epithelium which shows gradations ranging from stratified squamous through stratified cuboidal to ciliated stratified low-columnar type. It is suggested that the epithelium lining the transitional zone is identical with the "intermediate epithelium" in the mouse nasopharynx and larynx.

Animals↗

Concept of the existence of human papillomavirus (HPV) DNA in histologically normal squamous epithelium of the genital tract should be re-evaluated.

Because of the crucial importance of guiding current thinking in the field of HPV epidemiology, the concept of the existence of HPV DNA in histologically normal squamous epithelium was re-evaluated. A series of 102 randomly collected cervical punch biopsies, previously proved to contain the DNA of HPV types 6, 11, 16, 18, 31 or 33 by in situ hybridization were subjected to analysis for the localization of HPV DNA, i.e., whether found in the normal epithelium or at the lesion site only. This material consisted of a representative series of flat, endophytic and papillary HPV lesions with all histological grades from HPV-NCIN to HPV-CIN III, and the six HPV types in the same proportions as they occur in non-selected series of HPV lesions. Weak signals of HPV DNA were found in the basal cells in 6/102 (5.8%) of the biopsies. HPV DNA was constantly present in the parabasal cells in 25/102 (25.4%), in the intermediate cell layers in (98/102, 96%), and in the superficial cells of all 102 lesions. Noteworthy was the constant failure to reveal even weak signals of HPV DNA (of any of the six types) in histologically normal squamous epithelium of any of the 87 lesions, where such an epithelium was detectable. The present findings confirm our previous 'impression' that HPV DNA rarely if ever appears in the histologically normal squamous (or columnar) epithelium in the genital tract, when analysed using the in situ hybridization. Thus, great care should be exercised in interpreting results that suggest the discovery of HPV DNA in normal genital tract epithelium, unless based on firm documentation by in situ hybridization.

Cervix Uteri↗

Culture and characterization of rat middle-ear epithelium.

This study was performed to design a method for the culture of rat middle-ear epithelium and to apply the method to investigate the characteristics of this epithelium. Culture of explants of middle-ear epithelium in the presence of the epidermal growth factor was successful, whereas serial cultivation required 3T3 feeder cells in addition to the epidermal growth factor. Cultured middle-ear epithelium was studied by phase-contrast microscopy, transmission and scanning electron microscopy, and combined light and scanning electron microscopy (LM/SEM). These techniques showed similarity between the cultured and the natural middle-ear epithelium. Explants and outgrowths showed both flat polygonal and ciliated epithelial cells. In serial cultivation, however, only the first of these cell types was observed. Frequently, a single primary cilium was found on the cell surface. Transmission electron microscopy showed cross-linked envelopes whose formation was promoted by ionophore X537A. Cytokeratin was demonstrated by immunoblotting, immunofluorescence, and immunoperoxidase methods, using an anti-cytokeratin monoclonal antibody. The model described here permits study of the differentiation of middle-ear epithelium in vitro and may be of future value for the study of chronic middle-ear diseases.

Animals↗

Localization of epidermal growth factor receptor in alveolar epithelium during human fetal lung development in vitro.

Epidermal growth factor (EGF) enhances alveolar type II cell differentiation. In human fetal lung explants, EGF stimulates surfactant protein A (SP-A) synthesis. This effect may occur through a direct interaction of the ligand on EGF receptors located within distal pulmonary epithelium during alveolar type II cell differentiation. To determine if EGF receptor is present in alveolar epithelium, immunostaining for EGF receptor and in situ hybridization for EGF receptor mRNA were performed in human fetal lung explants undergoing alveolar type II cell differentiation in vitro. After 4 days in culture, EGF receptor immunostaining was present in alveolar epithelium from human fetal lung explants compared to minimal immunostaining in undifferentiated human fetal lung epithelium prior to culture. In situ hybridization revealed increased EGF receptor mRNA in differentiated type II cells from cultured explants, with minimal EGF receptor mRNA detected in undifferentiated epithelium from tissue prior to culture. Immunogold staining revealed EGF receptors on the cytoplasmic membranes of epithelial cells lining the prealveolar ducts in human fetal lung explants after 2 days in culture. Alveolar type II cell differentiation in vitro was confirmed ultrastructurally by the presence of lamellar bodies and biochemically by an increase in SP-A content. Thus, EGF receptor is found in alveolar epithelium during differentiation, which suggests an important role for EGF during human fetal lung development.

Embryonic and Fetal Development↗

Cholinergic stimulation of phosphatidylinositol hydrolysis by rat corneal epithelium in vitro.

Phosphatidic acid (PA) is an obligate intermediate in the phosphatidylinositol (PI) cycle and may serve as a sensitive marker for this pathway of reactions. Previously, we have shown that acetylcholine (ACh) stimulates formation of labeled PA in whole rat corneas whose phospholipids were prelabeled with [14C]arachidonate. To determine which layer of the cornea exhibits the ACh effect, intact epithelium was isolated from the rest of the corneal tissue (designated "stroma/endothelium") by incubating rat corneas with neutral protease and then stripping off the epithelium using forceps. The epithelium was ultrastructurally normal and avidly incorporated [14C]arachidonate into phospholipids; the stroma/endothelium had only trace incorporation. [14C]Arachidonyl-PA formation by the epithelium was significantly increased after a 37 second (+58%) and was maximal after a 5.0 minute (+188%) incubation in the presence of 1 mM ACh. The stimulation by ACh was blocked by atropine and scopolamine but not by d-tubocurarine. The epithelium also incorporated significant quantities of [3H]inositol into phosphatidylinositol (PI), phosphatidylinositol monophosphate (PIP), and phosphatidyl-inositol bisphosphate (PIP 2). When [3H]inositol-labeled epithelia were incubated for 5 minutes with 1 mM ACh, [3H]inositol monophosphate (IP) was increased 200%, [3H]inositol bisphosphate (IP2) was increased 225%, and [3H]inositol 2 trisphosphate (IP3) was increased 74%. These results suggest that muscarinic cholinergic receptors may be an important regulator of the PI cycle in corneal epithelium and thus may affect intracellular calcium mobilization and epithelial proliferation and regeneration.

Acetylcholine↗

Gene expression profile differences in gastric cancer, pericancerous epithelium and normal gastric mucosa by gene chip.

AIM: To study the difference of gene expression in gastric cancer (T), pericancerous epithelium (P) and normal tissue of gastric mucosa (C), and to screen an associated novel gene in early gastric carcinogenesis by oligonucleotide microarray. METHODS: U133A (Affymetrix, Santa Clara, CA) gene chip was used to detect the gene expression profile difference in T, P and C, respectively. Bioinformatics was used to analyze the detected results. RESULTS: When gastric cancer was compared with normal gastric mucosa, 766 genes were found, with a difference of more than four times in expression levels. Of the 766 genes, 530 were up-regulated (Signal Log Ratio (SLR) >2), and 236 were down-regulated (SLR<-2). When pericancerous epithelium was compared with normal gastric mucosa, 64 genes were found, with a difference of more than four times in expression levels. Of the 64 genes, 50 were up-regulated (SLR>2), and 14 were down-regulated (SLR<-2). Compared with normal gastric mucosa, a total of 143 genes with a difference in expression levels (more than four times, either in cancer or in pericancerous epithelium) were found in gastric cancer (T) and pericancerous epithelium (P). Of the 143 genes, 108 were up-regulated (SLR>2), and 35 were down-regulated (SLR<-2). CONCLUSION: To apply a gene chip could find 143 genes associated with the genes of gastric cancer in pericancerous epithelium, although there were no pathological changes in the tissue slices. More interesting, six genes of pericancerous epithelium were up-regulated in comparison with genes of gastric cancer and three genes were down-regulated in comparison with genes of gastric cancer. It is suggested that these genes may be related to the carcinogenesis and development of early gastric cancer.

Epithelium↗